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We used diffusion-tensor cardiac MR to investigate myocardial microstructure changes, including tissue integrity (mean diffusivity [MD], fractional anisotropy) and fiber architecture (helix angles) in patients with recent myocardial infarction (MI). This study aimed to investigate the sequential changes of myocardial microstructure and its relationships with changes of macrostructure and function of the left ventricle post-MI.Seventeen patients (age, 55.1±11.5 years; all men) participated in the follow-up study. Diffusion-tensor cardiac MR, cine gradient echo for left ventricle function, and late gadolinium enhancement for viability were measured from recent to chronic MI (median interval, 191 days). When compared with the remote zone, the infarct-adjacent zone showed overall increase of MD (2-way MANOVA, F1,16=36.3; P<0.001), decrease of fractional anisotropy (F1,16=5.8; P=0.029), and decrease of mean helix angles (F1,16=62.0; P<0.001). From recent to chronic MI, there was overall sequential decrease of MD (F1,16=22.6; P<0.001) and increase of fractional anisotropy (F1,16=7.8; P=0.013). Multiple linear regression showed that the improvement of wall thickening in the infarct-adjacent zone correlated with sequential decrease of MD in the infarct-adjacent zone (r=−0.70; P=0.002) and increase of mean helix angles (ie, more right-handed helical myofiber reorientation, predominantly subendocardial location) in the remote zone (r=0.60; P=0.011). Likewise, wall thickening in the remote zone correlated with MD in the remote zone (r=−0.72; P=0.001) and mean helix angles in the infarct-adjacent zone (r=0.72; P=0.001).Diffusion-tensor cardiac MR suggests that sequential zonal improvement of tissue integrity and fiber architecture remodeling both associate with sequential recovery of zonal wall thickening of the left ventricle from recent to chronic MI.