Synchrotron-based X-ray phase contrast imaging of transmural cardiac tissue in patients treated for advanced heart failure

Abstract

Abstract Background Cardiac imaging is essential for identifying structural changes in advanced heart failure (HF) and understanding underlying pathophysiology. Synchrotron radiation-based X-ray phase contrast imaging (X-PCI) is a non-destructive imaging modality that can provide high resolution three-dimensional (3D) visualisation of cardiac tissue on the microstructural level. Thus far, such analyses including the quantification of myocyte aggregates ranging from the epicardium to the endocardium, have been confined to animal models and human fetal tissue. We aimed to explore the feasibility of using X-PCI to quantify and compare structural organisation and orientation of myocyte aggregates in the myocardium across different advanced HF aetiologies. Methods and design Four adult patients were included - two receiving a left ventricular assist device (LVAD), and two undergoing heart transplantation (HTx). Aetiology of advanced HF in both the LVAD and HTx group was ischaemic heart disease and dilated cardiomyopathy (DCM), respectively. Transmural tissue samples were obtained by left ventricular apical coring (LVAD) and from the explanted hearts (HTx). The tissue specimens were imaged by X-PCI at the TOMCAT beamline using an effective pixel size of 5.8 µm. Orientation of aggregates of cardiomyocytes was assessed using a structure tensor-based method and morphological parameters were derived - the helical angle (HA), or the angle between the circumferential left ventricular plane and myocyte aggregates, and fractional anisotropy (FA), the degree of anisotropy or disorganisation of the local myocardium. Results The general patient characteristics are shown in Table 1. X-PCI enabled 3D visualisation of transmural myocardial tissue samples showing differences in organisation of myocardial structure in different HF aetiologies (Figure 1). The epicardial adipose layer was thicker in DCM, paired with a thinner epicardial myocyte layer (yellow arrows). Furthermore, the epi-to-endocardial HA transition was clearly visualized in ICM (double arrows), whereas there was clear disruption of the HA gradient in DCM samples – a finding further quantified via FA (green arrows). Conclusion X-PCI allows non-destructive advanced imaging of ex-vivo tissue. By harnessing the power of digital 3D imaging on a cellular level, it provides a novel insight to differential information on tissue organisation in different aetiologies of advanced heart failure.Table 1Figure 1