Characterizing cardiac involvement in amyloidosis using cardiovascular magnetic resonance diffusion tensor imaging

Abstract

Background: In-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls.

Methods: Ten patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A).

Results: MD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10^{- 3} vs 1.41 ± 0.07 10^{- 3} mm²/s, p < 0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p < 0.001). MD demonstrated an excellent correlation with native T1 (r = 0.908, p < 0.001) while FA showed a significant correlation with ECV in the CA population (r = - 0.851, p < 0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain (r = 0.921, p < 0.001).

Conclusion: CMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA.

Keywords: Cardiac amyloidosis; Cardiovascular magnetic resonance imaging; Diffusion tensor imaging; Myocardial microstructure; Tissue characterization.

Fig. 1

Representative mean diffusivity (MD), fractional anisotropy (FA) and native T1 maps for a healthy control (a) and a light chain (AL) amyloidosis patient (b). Enhanced T1 mapping, extracellular volume fraction (ECV) mapping and late gadolinium enhancement (LGE) CMR imaging was only performed in the cardiac amyloid (CA) patient. It can be appreciated, that the areas of signal hyperenhancement in LGE and elevated ECV correspond well with regions of high MD and low FA in the parameter maps derived from CMR diffusion tensor imaging (DTI) in the CA patient

Fig. 2

Correlation plots for MD and FA with native T1 and ECV. Native T1 shows an excellent correlation with MD (a) and a moderate but still significant negative correlation with FA (b). Within the patient population, MD is also correlated with ECV (c) but FA exhibits a higher correlation with ECV (d)

Fig. 3

Example helix angle (HA), transverse angle (TA) and sheet angle (E2A) map for a healthy control subject and an AL-amyloidosis patient (a). Image (b) shows Bullseye plots for HA, TA and E2A across all subjects for each cohort. Reported values are mean ± SD

Fig. 4

Correlation plots for GLS with HA slope and E2A sheet angle. The HA slope shows an excellent correlation with GLS (a) while a moderate but still significant correlation between GLS and E2A could be observed (b)