How hierarchical phase contrast tomography will change medical practice

An exciting new imaging technology promises a look at the tissues of the body with a resolution 10 times greater than a medical CT scanner.

Biological tissues are ineffably complex. They consist of individual specialized cells layered in organotypic functional units. Three-dimensional spatial relationships, morphology, and interplay spanning various lengths allow for physiologic function.

An emerging technology—a prototype x-ray technique called hierarchical phase contrast tomography (HiP-CT)—decouples field of view and resolution to yield images of the human body at the micron level. The 3D map of intact organs at cellular magnitude could proffer a foundational comprehension of system-level interactions intrinsic in pathology.

Let’s take a closer look. 

HiP-CT

Current hierarchical imaging strategies involve physical subsampling to produce high-resolution images. Using subsampled data, however, is imperfect, according to the authors of an article published in Nature Methods.

“Physical subsampling creates challenges in data registration and the requirement that correct or representative subsamples are collected,” the authors wrote. “New 3D imaging techniques are therefore required to bridge length scales from spatial relationships at the cellular level to the architectural organization of intact human organs.”

To overcome these limitations, the authors developed HiP-CT.

HiP-CT is an x-ray phase propagation technique that uses the Extremely Brilliant Source, which is a particle accelerator located in France. This particle accelerator is currently the brightest source of x-rays—100 billion times brighter than a hospital x-ray to be exact. 

Combined with beamline equipment, sample preparation, and scanning advances, investigators are able to perform cellular 3D scans of organs without destroying human tissue at any level of the body.

Using HiP-CT, the whole body is scanned at a resolution of 25 microns, which is 10 times the resolution of a regular medical CT and thinner than a human hair. These images can then be zoomed in on to attain micron-level resolution, or 100-fold greater resolution than ordinary CT. 

Applications

Although still in the experimental stages, the authors of the Nature Methods study highlighted intriguing uses of HiP-CT that could revolutionize medicine. They applied the technology to lung, brain, heart, kidney, and spleen tissue. They zoomed in on the structural overview to yield multiple higher-resolution volumes, thus visualizing organotypic functional units, as well as specialized cells. The investigators visualized individual glomeruli in the kidneys. They also visualized changes in tissue structure in the lung of a patient who died from COVID-19.

“HiP-CT has considerable translational potential for biomedical applications, which we demonstrated by the 3D imaging of a SARS-CoV-2-infected lung,” they wrote. “In addition to reproducing the histopathological hallmarks of COVID-19, HiP-CT revealed extensive regional heterogeneity in parenchymal damage.”

The authors noted that the quantitative assessment of architecture from HiP-CT images confirmed observations that a higher volume of ventilated air does not play a role in gas exchange in COVID-19-related ARDS. Such results could be augmented by machine learning. On a related note, HiP-CT could be used to examine COVID-19 complications in the kidney and brain.

Discussing these same applications in a separate paper published in bioRxiv, the authors wrote: “Further HiP-CT investigation of COVID-19-related ARDS requires refinement of tools for unbiased feature extraction from scans. We have begun to implement such methods, for example, by training and validating a 3D convolutional neural network for automated detection of airway, vascular or parenchymal elements in HiP-CT scans and radiomics for high-throughput extraction of radiographic features naked to the human eye.”

Bottom line

HiP-CT represents a cutting-edge technology that allows the user to image the body at the cellular level. By zooming into a CT image, resolution is 100 times greater than normal CT scans. Although still a prototype, this machinery promises to revolutionize the understanding of pathology and augment diagnosis and treatment.

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