X-ray tomography helps understand how the heart beats

Researchers at the Swiss Light Source SLS’s TOMCAT beamline have used phase contrast X-ray imaging to study a rat’s heart as it beats. The work will pave the way to investigations into how the heart beats on a cellular level, and understanding the effect of disease and drugs on the cardiac cycle.

How the heart beats on a cellular level is not fully understood. By using tomographic X-ray phase contrast imaging at the SLS, researchers can investigate how the cellular structure changes while a heart beats.(Image: AdobeStock)

How the heart works may be the subject of a high school biology class. But how it really works on a cellular level is in fact not fully understood. The muscle cells that make the heart contract are called cardiomyocytes. Central to their function is their three dimensional arrangement in the muscular walls of the heart, which evolves throughout the cardiac cycle. As the heart beats, the cardiomyocytes aggregate and orientate themselves into fibres in such a way that determines the propagation of electrical currents and thus the force generated within the heart. However, how this process really takes place remains unknown, as most experimental techniques do not allow something as small as a cell to be evaluated while they function within the organ.

Here, in steps the Swiss Light Source's TOMCAT beamline with phase-contrast tomographic X-ray imaging. This technique gives the advantage of multiscale imaging: allowing something very small (the cellular structure) to be studied in something very big (the heart). Now, thanks to a specially designed perfused isolated heart system (‘Langendorff’), a team of researchers were able for the very first time to study the heart in action as it beats at an unprecedented resolution. “This system combined with the ultra-fast endstation that we have at the TOMCAT beamline allows us to make dynamic measurements, giving us unique access to how the heart is beating,” says TOMCAT beamline scientist Anne Bonnin, who leads the project in collaboration with colleagues in Bern and Barcelona.

Because you have access to how the cardiac fibres change over time, you can foresee different types of studies: for example, what happens if the heart has a stroke or if we ingest certain drugs

Anne Bonnin, TOMCAT beamline scientist

A Langendorff heart compatible with X-ray tomography

The Langendorff system keeps the heart beating after it has been removed from the circulatory system of the donor – in this case, a rat. This is achieved by perfusing the heart with nutrient rich, oxygenated buffer solutions under carefully controlled conditions. The team created a customised Langendorff system, notably that can rotate, which it is compatible with phase contrast tomographic X-ray imaging. Using their set up, the team were able to record the heart beating in three dimensions at an unprecedented resolution and observe the changing cardiomyocyte aggregates and other larger cardiac structures.

In a part of the heart where the left ventricular wall (LV), septum (S) and right ventricular wall (RV) meet, the researchers could observe how the cardiomyocyte aggregates (shown by red arrows) change during the cardiac cycle. The yellow arrows indicate arterial blood vessels.(Image: Original publication by H.Dejea et al. Frontiers in Cardiovascular Medicine, 2022 (see below))

A high-resolution means to study how drugs and disease affect the cardiac cycle

Now that the feasibility of the system has been demonstrated, the work paves the way to high-resolution studies on the dynamics of the heart structure, including diseases or drugs that affect this, as Anne Bonnin explains. “Because you have access to how the cardiac fibres change over time, you can foresee different types of studies: for example, what happens if the heart has a stroke, how it differs with different heartrates or what happens if we ingest certain drugs.”

The SLS 2.0 upgrade, during which TOMCAT is set to receive a phase-I beamline upgrade in 2025, promises to be a game-changer for this work. At present, Bonnin comments, the field of view only covers a small part of the heart at a time. The higher coherence and flux of SLS 2.0 combined with the beamline upgrade will make it possible to improve the image quality drastically and achieve image of an entire heart cross section. Indeed, higher coherence will provide greater contrast – a crucial factor for the phase contrast X-ray imaging team, who rely on the phase changes of a coherent beam in different materials.

Text: Paul Scherrer Institute / Miriam Arrell