Multidimensional Analysis of the Adult Human Heart in Health and Disease using Hierarchical Phase-Contrast Tomography (HiP-CT)

Abstract

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one ‘control’ without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac ‘blueprint’ with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.

The Atrioventricular Conduction Axis Revisited for the 21st Century

“…The technique of microcomputed tomography satisfies these requirements, but also requires the heart being analysed to be immersed in a contrast solution so as to distinguish the conduction axis from the adjacent working myocardium [50]. The alternative techniques of multiscale and hierarchical phase contrast tomography, abbreviated to HiP-CT [51,52], will avoid the need to immerse the specimen under investigation in potentially damaging solutions. The use of these new forms of anatomic imaging, furthermore, will make it possible to reconstruct the heart and then section it in any required plane and at a high resolution, allowing the cellular make-up of the components of the conduction axis to be shown in the three orthogonal planes and revealing the location of the axis with absolute precision relative to the boundaries of the pyramid of Koch.…”

“…As more hearts are interrogated, it should prove possible to resolve additional problems, such as the precise dimensions of the potential pathways for atrioventricular nodal re-entry tachycardia. As already suggested by those describing the initial results [52], the HiP-CT technique truly has the capacity to be the game-changer required to show the precise arrangement, locations, and variability of the atrioventricular conduction axis.…”