Increasing the resolution, the scale takes the scanner and the diagnosis to a higher level

To diagnose and treat diseases such as cancer, scientists and doctors need to understand how cells respond to different disease states and treatments. The researchers have developed a new way to study diseases at the cellular level.

Dr. Keith Cheng, a distinguished professor of pathology, pharmacology, biochemistry, and molecular biology at Penn State College of Medicine, and a team of X-ray physicists from the University of Chicago, have developed a new technique. Three-dimensional tissue imaging, called X-ray histotomography. The technique allows researchers to study the cell details of a tissue sample without having to slice it. And this could lead to better diagnoses and treatments for various diseases, including cancer.

"Quantitative and objective measurements made possible by histotomography could potentially allow us to distinguish cancer subtypes from other diseases that are currently similar by using traditional histology so that they can be treated more appropriately, "said Cheng.

Traditional histology involves taking thin slices of tissue from patients, staining them, and examining them with a magnifying glass to look for irregular features under a microscope. The physical cut of the sample introduces tissue loss and distortion that leads to incomplete sampling and imperfect visualizations. According to the researchers, X-ray histotomography avoids these problems and makes it possible to accurately measure the three-dimensional characteristics of cells such as shape and volume.

For more than 10 years, Cheng and his team have developed the technique by combining the principles of computed tomography (CT) and histology to image small organisms and tissues at higher resolution in 3D.

"The X-ray histotomography uses the same principles as the human scanner," said Cheng. "CT is taking a series of x-rays of a subject, each from a slightly different angle.A computer program then uses the entire x-ray to create a 3D image."

Cheng's laboratory had previously used micro-CT, a smaller-scale version of human tomodensitometry, to image small organisms and tissues. Patrick La Rivière, associate professor of radiology at the University of Chicago, initiated Cheng with the use of a powerful X-ray source, the synchrotron, which allowed the team to research to improve their computed tomography with increased resolution and faster imaging times. Synchrotron-based micro-CT could help pathologists answer questions such as:

• What are the individual characteristics of the patient's disease?
• How many sick cells are there?
• What are the individualized treatment options based on what I see?

The technology needed to answer questions such as these was not commercially available, Cheng said, so that he and a team of engineers, physicists, data scientists and biologists undertook to develop them. the technique itself.

After a decade of optimizing the preparation and imaging of the samples, the team created 3D reconstructions of young zebrafish that could be examined from the entire organism up to the end of the day. cellular level. Zebrafish has been chosen to develop this technology because its size, from larvae to adults, is almost identical to the samples used by doctors to evaluate cancerous tumors.

According to Cheng, researchers and clinicians can now look at features such as 3D shape, volume, location and number of cells that previously could not be studied with the aid of histology traditional. The technique will allow pathologists to study a complete sample of tissue after it has been stained and prepared. It is no longer necessary to cut a single slice of fabric from the entire sample.

Clinical scientists can evaluate the microscopic and three-dimensional characteristics of cells because of the increased clarity and resolution of images.

"The beauty and complexity of the fabric I saw were mind-blowing," Cheng said of the newspaper images. eLife with research on June 11th.

Computational tools combined with imaging can calculate and catalog the size, shape, volume and density of cells. This ability makes it possible to study the characteristics of the pathology of the disease in a new way, likely to improve clinical care and facilitate drug discovery.

Advances in computer technology make it possible to process and visualize zebrafish large image files (100 gigabytes each). Researchers can simultaneously examine the characteristics of the disease at the level of the organic system, tissues or cells, slice by slice or in a 3-D context. They may even be able to see and interact with the cellular structure of organisms using the same technology used by players in virtual reality.

Cheng's future research team aims to increase the resolution, sample size, throughput, analytical power and accessibility of the technique.