New technology enables holistic images of deep living tissue for the first time

A new device that uses light to non-destructively image tissue could revolutionize cartilage and tissue transplant surgery, laying the foundation for treating osteoarthritis.

Published on September 9 in Nature CommunicationsResearch from King’s College London, the University of Southern Denmark and Boston University unveils a new device capable of showing the molecular structure of deep tissues without using limiting fluorescent labels, the first of its kind.

The new, readily available machine could help increase the use of tissue engineering in medicine and cut the costs of producing tissue in the lab in half.

Tissue engineering involves restoring or improving the function of cells and tissues in the body by replacing their defective counterparts with cells grown in the laboratory. This technique has the potential to be used in a wide range of applications, such as growing cartilage to transplant into a patient’s damaged knee. Cartilage has no way of replacing itself, and damage to it is the primary cause of osteoarthritis.

The composition of transplanted cells and tissues is critical to the body’s acceptance of them. If the internal composition of the tissue is compromised, it is more likely to be rejected or to function poorly. This is particularly true of the extracellular matrix, the area between cells that governs cell structure and how cells communicate with each other.

To assess this area, traditional imaging methods such as fluorescence microscopy have used fluorescent markers to label specific molecules within the cell. In addition to providing a limited view, by only collecting information from groups of labeled molecules, these markers can be toxic. This prevents transplantation of the tissue.

In tissue engineering, this means that two sets of tissue cultures must be grown in the laboratory before they can be transplanted into the body, one to be examined to see if the sample is safe, and the other for transplantation.

As well as being an expensive procedure, the wide variation in the quality of the composition of cells grown in the lab means that even if scientists take images of a sample made under the same conditions as the one they plan to transplant into the body, they cannot be certain that it will not be rejected.

The researchers’ approach, Raman spectral projection tomography, builds on previous technologies that use light to provide a clear, noninvasive view at a much deeper level than previously possible, assessing the extracellular matrix.

Dr Mads Bergholt, Senior Lecturer in Biophotonics at King’s College London, said: “Tissue engineering has the potential to change the lives of many patients. Around 1 in 5 people aged 45 in the UK have osteoarthritis, and knee cartilage has no way of replacing itself. Transplantation using tissue-engineered structures could help solve this problem.”

“However, the composition of most lab-grown cartilage has varying levels of vital components in the extracellular matrix, such as collagen. Without being able to observe this variation, scientists can never be certain that the tissues they transplant into the body will be safe and functional, and steps taken to improve individual samples will be slow and iterative.

“By visualizing these tissues without killing the cells, for the first time, researchers will be able to be certain that a transplant will work for half the cost.”

In the future, the team hopes to use this technology in operating rooms to image tumors in patients undergoing operations to remove them, reducing the need for time-consuming study of tumor tissue while potentially saving time and lives.

Dr. Martin Hedegaard Ph.D., Associate Professor of Biophotonics at the University of Southern Denmark, said: “This system opens up several possibilities for tissue imaging not only in tissue engineering, but also in cancer and autoimmune disease applications.

“For the first time, Raman technology is not just a surface-sensitive technology. We can now see through larger tissues with real spatial information about where specific signals are coming from. This would be valuable for understanding the spread of cancers and the progression of autoimmune diseases such as rheumatoid arthritis.”