Revisiting the Structure of the Ventricular Myocardium in Tetralogy of Fallot Using Hierarchical Phase Contrast Tomography and Structure Tensor Analysis

BACKGROUNDIn tetralogy of Fallot (ToF), changes to right ventricular (RV) function (as seen by strain or TAPSE) relate to altered myocardial structure. Direct three-dimensional anatomical evidence supporting these changes remains limited. OBJECTIVESTo non-destructively characterize myocardial architecture in pediatric ToF hearts using Hierarchical Phase-Contrast Tomography (HiP-CT) and structure tensor analysis. METHODSTwenty ToF and control pediatric hearts were imaged at the European Synchrotron, ESRF. Myocyte orientation was assessed through structure tensor analysis and distributed high-performance computing. A region-specific framework was developed for analysis of the RV. The predominant direction of myocardial aggregates (their helical angle) was compared across ventricular regions. RESULTSSignificant differences in orientation were found in all ToF segments vs controls (left ventricle, RV inlet, RV outflow tract, septum; p < 0.001). Myocytes in the ToF RV inlet were more circumferential overall, with regional heterogeneity. Contrary to traditional models, no discrete middle layer was found in the ToF RV, instead, a shift towards more circumferentially orientated myocytes and disrupted septal and outflow components was observed. RV contribution to the septum was greater in ToF (47.3% vs 34.0% ; p = 0.0026) with extension of ventricular insertion points disrupting septal architecture. There were more longitudinally oriented myocytes in the ToF RVOT, consistent with hypertrophied septo-parietal trabeculations. LV structure in ToF demonstrated a greater proportion of circumferentially oriented myocytes vs controls. CONCLUSIONSWe reveal profound alterations in ToF myocardial organization which broadly align with clinical observations and provide the first open-access HiP-CT congenital heart disease data as a basis for future computational modelling.