The method could be a route to faster, less invasive cancer diagnoses.
As an organism grows, so does its feeling. In the early stages, an embryo assumes an almost fluid-like state that allows its cells to divide and expand. As it matures, its tissues and organs consolidate into their final shape. In certain species, this physical condition of an organism can be an indicator of its stage of development and even of its general state of health.
Well, researchers from
MIT is an acronym for the Massachusetts Institute of Technology. It is a prestigious private research university in Cambridge, Massachusetts founded in 1861. It is divided into five faculties: architecture and planning; Mechanical engineering; Humanities, arts and social sciences; Administration; and science. MIT’s influence includes many scientific breakthroughs and technological advances.
“> MIT have found that the arrangement of the cells of a tissue can serve as a fingerprint for the“ phase ”of the tissue. They developed a method to decipher images of cells in a tissue in order to quickly determine whether that tissue is more solid, liquid, or even gaseous. Their results were recently published in the Proceedings of the National Academy of Sciences.
The team hopes their method, which they have called “configurative fingerprinting,” can help scientists track the physical changes in an embryo as it develops. Immediately they use their method to examine and ultimately diagnose a certain type of tissue: tumors.
In cancer, there is evidence that, like an embryo, the physical condition of a tumor can indicate its stage of growth. Tumors that are more solid can be relatively stable, while more fluid-like growths might be more prone to mutation and metastasis.
MIT researchers analyze images of tumors that have been both grown in the laboratory and biopsied from patients to identify cellular fingerprints that indicate whether a tumor is more solid, liquid, or gas. They envision that one day doctors could match an image of tumor cells with a cellular fingerprint to quickly determine the tumor phase and ultimately cancer progression.
“Our method would make it very easy to diagnose cancerous conditions by simply examining the position of cells in a biopsy,” says Ming Guo, associate professor of mechanical engineering at MIT. “We hope that doctors can tell directly from the location of the cells whether a tumor is very solid, that is, it cannot yet metastasize, or whether it is more fluid-like and a patient is at risk.”
Guo’s co-authors are Haiqian Yang, Yulong Han, Wenhui Tang and Rohan Abeyaratne from MIT, Adrian Pegoraro from the University of Ottawa and Dapeng Bi from Northeastern University.
In a perfect solid, the individual components of the material are arranged in an orderly lattice, like the atoms in a crystal cube. If you cut a slice of the crystal and put it on a table, you would see that the atoms are arranged so that you can connect them in a pattern of repeating triangles. Since the distances between atoms would be exactly the same in a perfect solid, the triangles that connect them would typically have an equilateral shape.
Guo took this construct as a template for a perfectly solid structure, with the idea that it could serve as a reference for comparing the cell configurations of actual, not entirely solid tissues and tumors.
“Real handkerchiefs are never perfectly organized,” says Guo. “They are mostly disorganized. But still there are subtle differences in how much they are disordered. “
Following this idea, the team started by taking pictures of different types of tissue and using software to map triangular connections between cells in a tissue. In contrast to the equilateral triangles in a perfect body, the maps produced triangles of various shapes and sizes that indicated cells with a range of spatial order (and disorder).
For each triangle in an image, they measured two key parameters: volumetric order, or the space within a triangle; and shear order, or how far the shape of a triangle is from the equilateral. The first parameter shows the density variation of a material, the second shows how susceptible the material is to deformation. They found that these two parameters are sufficient to characterize whether a tissue is more solid, liquid or gaseous.
“We calculate the exact value of both parameters directly in comparison to a perfect solid and use these exact values as our fingerprints,” explains Guo.
The team tested their new fingerprint technology in several different scenarios. The first was a simulation in which they modeled the mixing of two types of molecules, the concentration of which they gradually increased. For each concentration, they mapped the molecules into triangles and then measured the two parameters of each triangle. From these measurements they characterized the phase of the molecules and were able to reproduce the expected transitions between gas, liquid and solid.
“People know what to expect in this very simple system, and that’s exactly what we’re seeing,” says Guo. “This has demonstrated the efficiency of our method.”
The researchers then applied their method in systems with cells instead of molecules. For example, they watched videos recorded by other researchers of a fruit fly wing growing. With their method, they were able to identify regions in the developing wing that went from a solid to a more fluid state.
“As a liquid, this can help with growth,” says Guo. “How exactly this happens is still being investigated.”
He and his team also grew small tumors from cells in human breast tissue and watched the tumors grow into appendage-like tendrils – signs of early metastasis. When they mapped the configuration of the cells in the tumors, they found that the non-invasive tumors resembled something between a solid and liquid state, and the invasive tumors were more gas-like, while the tendrils showed an even more disordered state.
“Invasive tumors were more like vapor, and they want to spread and go anywhere,” says Guo. “Liquids can hardly be compressed. But gases are compressible – they can swell and shrink easily, and that’s what we see here. “
The team works with samples of human cancer biopsies, which they image and analyze to refine their cellular fingerprints. Finally, Guo envisions that mapping the phases of a tissue can be a quick and less invasive way to diagnose multiple cancers.
“Doctors usually have to take biopsies and then stain different markers depending on the type of cancer in order to make a diagnosis,” says Guo. “Perhaps one day we will be able to look inside the body with optical tools without touching the patient, in order to see the position of the cells and to say directly which cancer stage a patient is in.”
Referenz: „Configurational Fingerprints of multicellular living systems“ von Haiqian Yang, Adrian F. Pegoraro, Yulong Han, Wenhui Tang, Rohan Abeyaratne, Dapeng Bi und Ming Guo, 25. Oktober 2021, Proceedings of the National Academy of Sciences.
This research was supported in part by the National Institutes of Health, MathWorks, and the Jeptha H. and Emily V. Wade Award at MIT.