New Software Reveals Unprecedented Insights into Embryonic Heart Development

Researchers have created a new software program that offers previously unheard-of capabilities for viewing inside 3D pictures. Through its dynamic, interactive cutaway views, they were able to use optical coherence tomography (OCT) images to analyze the dynamics of mouse heart development that had never been seen before.

An improved understanding of heart development could help inform new clinical strategies in managing congenital heart diseases, which are the most common type of birth defects. Such insights are also foundational for designing innovative strategies of regenerating heart tissue after damage from a heart attack, improving the cardiac function.”

Shang Wang, Research Team Leader, Stevens Institute of Technology

The study was published in the journal Biomedical Optics Express published by the Optica Publishing Group. It is an easy-to-use tool for visualizing intricate structures in a single cutaway view, like a tubular structure that curves in three dimensions.

3D imaging already plays an essential role in biomedicine, but there’s still more we can learn if we consider the temporal aspect - that is, as a 4D image. Although we demonstrated the clipping spline with 4D OCT data, it can be used for volumetric images from any imaging modality, for both biological research and clinical medicine applications.”

Andre Faubert, Research Team Member and Research Associate, Stevens Institute of Technology

Visualizing Complex 3D Structures

The researchers created the clipping spline while the researchers were studying the cardiac looping stage of embryonic mouse heart development using 4D OCT images. The heart tube has a convoluted shape with significant structural and blood flow changes as it bends and twists.

“The looping stage is a vital stage of heart development and is responsible for a range of congenital defects. Little is known about the dynamics and processes that take place during this stage; although they can be imaged, there were only limited tools available to visualize and analyze them,” said Shang Wang.

To close this technological gap, the researchers created a new software tool that performs volume clipping, a computational method of removing specific voxels in a 3D image to reveal the structure of interest inside.

The software equivalent of cutting a solid object with a knife to see what is inside is called volume clipping. Performing volume clipping for intricate structures in a single cutaway view is difficult, though, and necessitates precisely defining the boundaries between the voxels to be removed and those to be retained.

Clipping planes, which function similarly to a straight knife cut, are currently the most widely used method for volume clipping. The inability to produce concave surfaces due to the basic planar geometry, however, restricts the capacity to fully depict complex structures in a single view. The researchers used the thin plate spline (TPS), a kind of smooth surface, to get around these restrictions and used it for volume clipping for the first time.

A set of control points defines the TPS, a three-dimensional surface that intersects each control point with the least amount of curvature. Users can interactively refine the surface's shape and position by moving, adding, or deleting control points, making it easy to adapt to complex structures.

Additionally, algorithmic transitions like moving, splitting, or merging control points are feasible because the TPS is defined using mathematical parameters. This enables dynamic visualizations like flythroughs and fluid 4D volume clipping.

The researchers also refined the computational pipeline for the clipping spline to create an effective, real-time tool for creating and modifying cutaway views into a volume.

Watching the Heart Develop

For instance, the researchers tracked myocardial dynamics over 12.8 hours of development across 712-time points using the clipping spline to visualize and analyze embryonic mouse heart development using OCT data.

The researchers were able to see more of the dynamics than before using the clipping spline, which allowed them to view several sections of the twisted heart tube simultaneously in a single view. The understanding of how the embryonic heart's biomechanics contribute to the creation of particular blood flow patterns improved as a result. The clipping spline was also used to reveal how the early heart's inflow tracts combine to form the sinus venosus, a structure that guides blood into the growing heart.

It is simply amazing to see these developmental processes taking place, and it inspires new thoughts and hypotheses that could lead to significant insights into how the mammalian heart develops. Studying and understanding biological development is not only essential for improving the clinical management of congenital diseases but is also foundational for many other biomedical areas, such as cancer and regenerative medicine.”

Shang Wang, Research Team Leader, Stevens Institute of Technology

According to the researchers, the clipping spline is prepared for broad adoption by the biomedical imaging community. The researchers are now concentrating on creating sophisticated image processing techniques with it and using them to learn more about the dynamics and mechanisms of the development of the embryonic heart.