Evaluation of myocardial microstructure in congenital heart diseases with diffusion magnetic resonance imaging

Abstract

New Zealand has a long history with studying congenital heart disease (CHD) and has one of the oldest collections of hearts that dates back to the 1950s. These pathological specimens can provide insight into the characteristics of CHD across particular patient groups. The work in this thesis details the development of MRI diffusion sequences and analysis techniques to assess myocardial fibre structure in these long-term fixed specimens. These techniques are then used to characterise the differences in fibre structure between specimens with different types of CHD. Tissues fixed in formalin for long periods of time have severely shortened T2. Commonly available diffusion imaging strategies on standard clinical MRI systems are unsuitable for use in these specimens. We developed and tested four candidate pulse sequences to overcome the limitations in short T2 specimens. A single spin echo pulse sequence using monopolar diffusion encoding gradients was found to be most suitable to provide the necessary diffusion weighting while minimise T2-related signal loss. After selecting an appropriate image acquisition strategy, a suitable post-processing pipeline to analyse the images and quantify cardiac diffusion metrics associated with fibre structure was required. We compared different regularization techniques using simulated cardiac diffusion imaging data to find a suitable techinque for the low-signal images expected from fixed specimens. Linear least-squares methods were found to be suitable to estimate cardiac diffusion metrics such as the helix angle, and transverse angle, even in noisy image data. We also present a technique for estimating the helix angle gradient across the heart wall and the asymmetry of the helix angle distribution. The acquisition and analysis techniques were subsequently used to assess the differences in fibre structure between different groups of CHD specimens. We assess the cardiac diffusion metrics in specimens with tetralogy of Fallot (TOF, n=10), dextrotransposition of the great arteries (dTGA, n=8), and systemic right ventricles (n=4). Two additional cases with unique pathology, one with situs inversus totalis and one with levo-transposition of the great arteries (lTGA) were also included. Our results show that the presence of ventricular septal defects (VSD) decrease the helix angle gradient in the septum, which is consistent with observations using other techniques. The presence of a VSD was also associated with a decreased helix angle gradient in the RV wall which correspond to the predominant circumferential fibres. In the TOF specimens, the helix angle gradient differed near the RV-LV junction and in the RV wall between cases with bicuspid or tricuspid pulmonary valves. The sheet angle in the septum of the TOF specimens was opposite to the sheet angles in the LV free wall. Systemic right ventricle had mainly circumferential myocytes. The helix angle variation in the single case of SIT was linear, asymmetric, and reversed until a transition zone near the epicardium. In conclusion, segment-wise myoarchitecture features in different types of heart defects could be associated with the cardiac dysfunctions that are observed clinically in congenital heart disease patients.