Tissue transparency technology is a method of making opaque tissue transparent in three dimensions by removing lipids from the tissue. This allows for high-resolution observation of cells and tissue structures, and CLARITY technology is particularly important for studying disease in the brain and organs.
The human brain is one of the most complex organs in the body. The number of neurons (the basic unit cells of the nervous system) in the brain is approximately 100 billion, which is similar to the number of stars in our galaxy, of which our solar system is a part. The human brain is so intricately connected with so many cells that its structure and function are not fully understood. The brain also plays a central role in regulating higher-order cognitive functions such as sensation, memory, learning, and thinking, and it plays an important role in constructing human identity. Therefore, understanding how the brain works is tantamount to understanding how we think, feel, and behave. To understand this complex biological system, we need to know the characteristics and functions of the cells that make up the brain, as well as their arrangement and connections, which means we need a high-resolution three-dimensional map, a blueprint of the human body with cellular-level resolution. Tissue transparency is a breakthrough technology for creating such high-resolution 3D maps.
Before we dive into what organizational transparency technology is, let’s take a look at how it came to be. Scientists have been trying to create high-resolution maps of the human body for organizational studies. Traditionally, tissues such as the brain have been imaged using methods such as computed tomography (CT), magnetic resonance imaging (MRI), or optical coherent tomography (OCT). These methods have been effective for studying structure and function because they allow for three-dimensional representation of living human tissue. However, the resolution is not high enough to show individual cell features or connections, and it is difficult to obtain molecular-level information. This is because the high density of cells creates a kind of barrier that prevents light and chemicals from entering the tissue. In particular, when the cells in human tissue are so densely packed, their lack of permeability makes it difficult to see detailed cell-to-cell interactions or neural network connectivity at a glance. Therefore, high-resolution microscopy, which can see down to the smallest cellular level in living tissue, is currently considered the most advanced method for creating three-dimensional maps.
However, when looking at large, opaque tissues such as the brain, high-resolution microscopy is limited by the need to image very thin slices of tissue. Thousands of two-dimensional images have to be recombined and stitched together into a three-dimensional map, which reduces the overall efficiency. A lot of research has been done to solve this problem, and recently, tissue transparency technology has been developed. In this context, the potential of tissue transparency technology is enormous. In life sciences research, precise imaging at the cellular and molecular level has opened up the possibility to further refine basic research and diagnosis of many complex diseases, including cancer, cardiovascular disease, and brain disorders.
Tissue transparency technology, which makes opaque tissues of organs transparent with special chemicals, has opened the way to overcome the limitations of high-resolution microscopy. The recently developed CLARITY technology enables observations with about 2,000 times the resolution of magnetic resonance imaging. CLARITY technology synthesizes a transparent, porous polymer net called a “hydrogel” within the tissue, preserving the tissue structure and molecules in three dimensions while completely removing the lipids that make the tissue opaque. In addition to making the tissue highly transparent, it also completely removes barriers that prevent light and molecular probes from penetrating, allowing light and molecular probes to easily penetrate the tissue. Despite the complete removal of barriers such as cell walls, the key to CLARITY technology is that the hydrogel preserves the three-dimensional information of the tissue at the molecular level, so the detailed morphology of the cells and the connections between them are well preserved.
As a result, CLARITY-treated tissues become optically transparent, allowing light to penetrate deeply, and even thick tissues such as the brain can be imaged directly with high-resolution microscopy without sectioning. Another advantage of CLARITY technology is the ability to image the three-dimensional distribution of specific molecules by staining the molecules in the tissue covalently linked to the hydrogel with organic dyes. The dyes can be removed without destroying the tissue structure or molecules, allowing for repeated analysis of different molecular phenotypes. This enables researchers to more vividly observe how cells and tissues interact in a living environment, and in particular, to capture changes within tissues during the development of certain diseases.
Furthermore, CLARITY technology can make most organs transparent, allowing for three-dimensional imaging, which can be used in brain science as well as for disease studies of organs through biopsy. In particular, CLARITY can be used to record the activity of specific disease-causing factors in organs in real time and the resulting tissue response. These advances will not only greatly expand the scope of medical and scientific research, but will ultimately play an important role in the development of precise medical techniques.
However, it’s not all rosy for CLARITY technology. There are still a few challenges that need to be addressed. The first is speeding up the process. Unlike analyzing thin sections, it takes months to process large samples such as mouse brains. This is because the process of delivering chemicals deep into the tissue to preserve, clarify, and stain it is very slow. Follow-up research is underway to solve this problem, and recent research in Korea on the Active Clarity Technique (ACT), which is up to 30 times faster than CLARITY, is showing promise. The second challenge is to reduce costs. The larger the size of the tissue to be analyzed, the more compounds are needed to make it transparent, as well as the amount of organic dyes, which are key to obtaining molecular information. The technical burden of processing large amounts of data also remains a challenge. Overcoming these low speed and high cost limitations will be the key to commercializing 3D mapping technology.
In this article, we have discussed the background of the development of organizational transparency technology, CLARITY technology, and the challenges. How will these CLARITY technologies impact humanity? Since Watson and Crick discovered the double helix structure of DNA, the Human Genome Project has sequenced genes to complete the human genetic map. Furthermore, CLARITY technology will contribute to the completion of a high-resolution map of the human body, which will answer the question of how the cells in which genes are expressed are connected to each other. Scientists are hopeful that with the development of these technologies, the secrets of the brain will be unlocked. In the near future, the structure and function of the brain’s nerve cells will be better understood, and intractable brain diseases such as Alzheimer’s and Parkinson’s will be cured.
