Three-dimensional micro-structurally informed in silico myocardium-Towards virtual imaging trials in cardiac diffusion weighted MRI.

In silico tissue models (viz. numerical phantoms) provide a mechanism for evaluating quantitative models of magnetic resonance imaging. This includes the validation and sensitivity analysis of imaging biomarkers and tissue microstructure parameters. This study proposes a novel method to generate a realistic numerical phantom of myocardial microstructure. The proposed method extends previous studies by accounting for the variability of the cardiomyocyte shape, water exchange between the cardiomyocytes (intercalated discs), disorder class of myocardial microstructure, and four sheetlet orientations. In the first stage of the method, cardiomyocytes and sheetlets are generated by considering the shape variability and intercalated discs in cardiomyocyte-cardiomyocyte connections. Sheetlets are then aggregated and oriented in the directions of interest. The morphometric study demonstrates no significant difference (p>0.01) between the distribution of volume, length, and primary and secondary axes of the numerical and real (literature) cardiomyocyte data. Moreover, structural correlation analysis validates that the in-silico tissue is in the same class of disorderliness as the real tissue. Additionally, the absolute angle differences between the simulated helical angle (HA) and input HA (reference value) of the cardiomyocytes (4.3°±3.1°) demonstrate a good agreement with the absolute angle difference between the measured HA using experimental cardiac diffusion tensor imaging (cDTI) and histology (reference value) reported by (Holmes et al., 2000) (3.7°±6.4°) and (Scollan et al. 1998) (4.9°±14.6°). Furthermore, the angular distance between eigenvectors and sheetlet angles of the input and simulated cDTI is much smaller than those between measured angles using structural tensor imaging (as a gold standard) and experimental cDTI. Combined with the qualitative results, these results confirm that the proposed method can generate richer numerical phantoms for the myocardium than previous studies.