Abstract
Diffusion tensor magnetic resonance imaging (MRI) reveals valuable insights into tissue histo-anatomy and microstructure, and has steadily gained traction in the cardiac community. Its wider use in small animal cardiac imaging in vivo has been constrained by its extreme sensitivity to motion, exaggerated by the high heart rates usually seen in rodents. Imaging of the isolated heart eliminates respiratory motion and, if conducted on arrested hearts, cardiac pulsation. This serves as an important intermediate step for basic and translational studies. However, investigating the micro-structural basis of cardiac deformation in the same heart requires observations in different deformation states.Here, we illustrate the imaging of isolated rat hearts in three mechanical states mimicking diastole (cardioplegic arrest), left-ventricular (LV) volume overload (cardioplegic arrest plus LV balloon inflation), and peak systole (lithium-induced contracture). An optimised MRI-compatible Langendorff perfusion setup with the radio-frequency (RF) coil integrated into the wet chamber was developed for use in a 9.4T horizontal bore scanner. Signal-to-noise ratio improved significantly, by 75% compared to a previous design with external RF coil, and stability tests showed no significant changes in mean T1, T2 or LV wall thickness over a 170 min period. In contracture, we observed a significant reduction in mean fractional anisotropy from 0.32 ± 0.02 to 0.28 ± 0.02, as well as a significant rightward shift in helix angles with a decrease in the proportion of left-handed fibres, as referring to the locally prevailing cell orientation in the heart, from 24.9% to 23.3%, and an increase in the proportion of right-handed fibres from 25.5% to 28.4%. LV overload, in contrast, gave rise to a decrease in the proportion of left-handed fibres from 24.9% to 21.4% and an increase in the proportion of right-handed fibres from 25.5% to 26.0%. The modified perfusion and coil setup offers better performance and control over cardiac contraction states.We subsequently performed high-resolution diffusion spectrum imaging (DSI) and 3D whole heart fibre tracking in fixed ex vivo rat hearts in slack state and contracture. As a model-free method, DSI augmented the measurements of water diffusion by also informing on multiple intra-voxel diffusion orientations and non-Gaussian diffusion. This enabled us to identify the transition from right- to left-handed fibres from the subendocardium to the subepicardium, as well as voxels in apical regions that were traversed by multiple fibres. We observed that both the mean generalised fractional anisotropy and mean kurtosis were lower in hearts in contracture compared to the slack state, by 23% and 9.3%, respectively. While its heavy acquisition burden currently limits the application of DSI in vivo, ongoing work in acceleration techniques may enable its use in live animals and patients. This would provide access to the as yet unexplored dimension of non-Gaussian diffusion that could serve as a highly sensitive marker of cardiac micro-structural integrity.
Highlights
Myocardial tissue structure is a key determinant of the mechanical and electrical properties of the heart in health and disease
The present study aims to (i) characterise the microstructure in rat hearts in multiple deformation states using diffusion magnetic resonance imaging (MRI), (ii) demonstrate how specialised hardware can improve the sensitivity of measurements and support more physiological conditions and (iii) show how a more comprehensive description of the diffusion profile expands our ability to characterise the microstructural properties of the heart
Images and Diffusion tensor imaging (DTI) parameter maps obtained from the 3-state protocol are shown in Fig. 3, where the slack state is taken to roughly represent diastole, the balloon-inflated state models increased venous return, and the lithium-induced contracture mimics end-systole
Summary
Myocardial tissue structure is a key determinant of the mechanical and electrical properties of the heart in health and disease. MRI data acquisition is typically sensitized to diffusion by adding pairs of magnetic field gradients to an imaging sequence (Stejskal and Tanner, 1965). Any diffusion that occurs along the axis of the gradients during the time interval between the pair of gradients leads to measurable signal attenuation due to imperfect reversal of phase, which is dependent on the water diffusivity, D, and the degree of diffusion weighting, described by the b-value (Le Bihan et al, 1991). As water diffusion is influenced by the presence of micro-anatomical structures, its measurement provides information on cell and tissue micro-architecture at a scale beyond the imaging resolution
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