type
status
date
slug
summary
tags
category
icon
password
Scientists have developed a new method to temporarily render tissue in living animals transparent for better optical imaging, which could be useful for medical and biological research because traditional optical imaging techniques are limited when viewing deep tissues by light scattering and absorption.
The researchers found that by dissolving a strong absorbing molecule in water (such as lemon yellow, a common food dye), the refractive index of water can be adjusted to match the tissue composition (such as fat) more closely, reducing the scattering of light in the tissue. In this way, the originally opaque skin, muscle and other tissues become temporarily transparent, allowing direct viewing of the structure and activity in the body.
They conducted experiments on mice, using a common food dye called tartrazine , which was dissolved in water and applied to the surface of mouse tissues. This method made the abdominal skin of the mice transparent, and the activity of intestinal neurons was observed. This technology does not require surgery and can perform high-resolution microscopic imaging directly on living animals, which is of great significance for biomedical research and diagnosis.
Technical principle
The research team found that by introducing a dye molecule that strongly absorbs ultraviolet and blue light bands, the refractive index in the long wavelength region (red light region) can be temporarily increased, thereby reducing light scattering in tissues and achieving optical transparency.
Theoretical Model
The study is based on the Lorentz oscillator model and the Kramers-Kronig relationship to explain how dye molecules change the refractive index of biological tissues, thereby achieving tissue transparency. Specifically:
- The Lorentz oscillator model
describes the response of electrons in dielectric materials to light. When dye molecules are dissolved in water, their absorption of light of different wavelengths affects the refractive index of the medium.
- The Kramers-Kronig relationship
is a physical relationship that connects the refractive index (real part) and the absorption coefficient (imaginary part) of a substance. When dyes are dissolved in water, they are able to change the refractive index of the aqueous medium to match that of tissue components such as lipids by strongly absorbing light in the blue region, thereby reducing light scattering.
Select dye molecules
The researchers chose Tartrazine as the dye molecule used in the experiment. Tartrazine is a common food dye with the following characteristics:
- Strong absorption ability: Tatrazine has strong absorption peaks in the ultraviolet and blue light bands of visible light (300 to 500 nanometers).
- Water Solubility: Tatrazine is easily soluble in water and therefore can be fully mixed with the aqueous medium in biological tissues.
- FDA Approval: Tatrazine has been approved by the U.S. Food and Drug Administration, ensuring its safety in experiments.
Experiments and Results
- Prepare dye solution: The research team used tatrazine solution and prepared an aqueous solution at a specific concentration so that it could effectively penetrate and act on living tissue.
- Organizational transparency experiment:
- Mouse experiments: The experiment showed that the tatrazine solution was able to successfully make the skin, muscles and connective tissue of mice transparent. After applying the solution, the tissue in the abdomen of the mice became transparent, allowing researchers to observe the organs and nerve structures in the body through a visualization system.
- In vitro tissue experiments: The dye solution also successfully achieved similar transparency in in vitro biological tissues (such as chicken breast) and tissue-mimicking hydrogel models. These models are used to simulate the optical scattering properties of biological tissues, further verifying the role of tatrazine solution in reducing light scattering.
Through the transparent abdominal area, researchers can observe the fluorescently labeled intestinal neural network and capture its dynamic activities related to intestinal peristalsis. This transparency effect is temporary, and the solution will naturally restore the tissue to its normal state after a period of time.
- Optical imaging experiment:
- Abdominal transparency experiment: By using tatrazine dye, the abdominal area of mice becomes transparent, enabling high-resolution optical imaging of deep organs, especially observing intestinal neural activity and peristalsis.The experiment demonstrated clear imaging of enteric neurons labeled with fluorescent proteins in mice, which provides an important tool for future monitoring of intestinal neural activity and functional research.
- Microscopic imaging: By applying tatrazine dye topically to the mouse scalp, the researchers successfully achieved high-resolution microscopic imaging of the mouse brain blood vessels. The brain blood vessel structure can be clearly seen after transparency.Similarly, the researchers applied tatrazine solution to the muscle tissue of mice and successfully performed microscopic imaging of muscle sarcomeres (the smallest contractile units of muscle fibers), demonstrating the ability to observe deep tissue structures with high resolution.
- Temporal and spatial resolution
- Time evolution graph: In the mouse abdominal transparency experiment, researchers used the transparency effect to record the time evolution graph of intestinal neural activity, showing the dynamic process of intestinal peristalsis and the movement patterns of different neurons.
- Spatial resolution: With this technology, the spatial resolution of imaging reaches the micron level, which can clearly capture the details of microscopic tissue structures while penetrating millimeter-level scattering media.
- Reproducibility and universality of the method
The experimental results showed that the tatrazine solution was not only effective in abdominal tissues, but could also be applied to different parts of the mouse, such as the head and hind limbs, to successfully achieve transparency and perform high-resolution imaging.The universality of this method is reflected in its successful application to different types of biological tissues, including skin, muscle, blood vessels, etc.
Technical Challenges and Limitations
- Scattering problem: Although the dye solution can significantly reduce light scattering, it cannot completely eliminate it, especially in the case of complex tissue structure and diverse components, a small amount of light scattering still exists.
- Duration of transparency: The effect of the dye solution is temporary and the duration of transparency is short, so repeated applications of the dye or improvements in the dye formulation may be required to extend the duration of action.
- Limited penetration depth: The diffusion depth of the dye affects the penetration depth of the clearing effect. In thicker tissues or organs, the dye may not penetrate sufficiently, thus limiting the imaging depth.
Application scenarios and extensions
The optical transparency of living tissues achieved by strongly absorbing molecules has broad application potential in the biomedical field. The following are the main application scenarios and possible future expansion directions of this technology:
Deep tissue imaging
This technology can make tissues transparent under non-invasive or minimally invasive conditions, thereby performing high-resolution imaging of deep tissues. This is of great significance for studying the internal tissue structure, neural activity, and organ function of organisms.
- Intestinal motility observation: By making the abdomen of mice transparent, researchers successfully observed the activity and motility of the intestinal neural network, which helps to study the physiological functions of the intestine, digestive system diseases, and the effects of drugs on the intestine.
- Nervous system imaging: By partially transparentizing the mouse head tissue, direct visualization of brain blood vessels and neuronal networks can be achieved, which is suitable for the study of neurological diseases such as Alzheimer's disease and Parkinson's disease.
High-resolution microscopy
This technology is suitable for observing the structure and dynamic activities at the cellular level, especially in complex tissues such as muscles, nerves, and blood vessels.
- Muscle microscopy: In the experiment, by making the mouse muscles transparent, microscopic imaging of the sarcomere (the smallest contractile unit of the muscle fiber) was successfully performed. This high-resolution observation is of great significance for the study of muscle diseases, motor dysfunction and regenerative medicine.
- Cerebrovascular imaging: The transparent scalp and vascular structures can be used to observe cerebral hemodynamics, which is suitable for early diagnosis and monitoring of brain diseases such as stroke and cerebrovascular disease.
Real-time function monitoring
After the tissue is transparent, the activities of deep organs can be monitored dynamically in real time, which is of great value for studying organ functions and their responses to external stimuli or drugs.
- Cardiac function imaging: By making the abdominal or chest area transparent, the heart beat and blood flow can be observed non-invasively, and heart function can be monitored in real time, which has potential applications in studying the pathological process of heart disease and the efficacy of drugs.
- Tumor monitoring: Transparent tissue technology can be used to observe tumor growth, angiogenesis, and changes in its microenvironment, and to track in real time the tumor's response to drugs during treatment, helping to optimize cancer treatment plans.
Tissue Clearance and Regeneration Studies
This technology provides a visualization tool for studying tissue clearance processes (such as the metabolic function of the liver and kidneys) and tissue regeneration, and can observe processes such as cell renewal and apoptosis within tissues.
- Regenerative medicine: This technology can be used to non-invasively monitor how cells repair damaged tissues during tissue regeneration, such as the regeneration of skin, muscle and bone. This is of great significance for research such as tissue engineering, stem cell therapy and wound repair.
- Organ clearance research: Transparent tissues can help study changes in the clearance functions of different organs (such as the liver and kidneys) under disease conditions and explore the mechanisms of organ damage and repair.
Drug development and efficacy evaluation
Transparent tissue technology can be used to evaluate the absorption, distribution, metabolism and excretion (ADME) of drugs in the body, as well as the direct effects of drugs on tissues and organs.
- Drug distribution observation: By making specific tissues transparent, the distribution of drugs in the body can be directly observed, and the concentration changes of drugs in different organs and tissues can be analyzed, providing key data for drug research and development.
- Drug efficacy monitoring: Transparency technology can observe tissue reactions after drug action in real time without destroying the tissue, helping to determine the optimal dose and route of administration, especially for evaluating the effects of anti-cancer and anti-inflammatory drugs.
6. Non-invasive disease diagnosis
Transparency technology makes non-invasive disease diagnosis possible, and pathological changes in internal organs or tissues can be directly observed through optical imaging technology.
- Tumor detection: Early detection of changes in tumor location, size, and morphology, especially deep-seated tiny tumors that are difficult to detect with traditional imaging methods.
- Diagnosis of neurological diseases: Transparent brain tissue can help monitor neuronal activity and hemodynamics in real time, providing support for the early diagnosis of neurological diseases.
Future expansion direction
Large Animal Models and Human Applications: Currently, this technology is mainly used in small animals (such as mice), and in the future it can be expanded to large animal models (such as pigs and monkeys), and even applied to humans. To this end, the safety, diffusion depth and transparency maintenance time of the dye need to be further optimized to meet the needs of larger tissue volumes.
Long-term transparency and dynamic monitoring: In order to meet the needs of long-term dynamic monitoring, future research needs to develop dyes that can prolong the transparency effect or improve the formula to ensure that the transparency remains stable during long-term experiments.
Versatile imaging technology combines: Combining clearing technology with existing imaging techniques (such as fluorescence imaging, confocal microscopy, ultrasound imaging, etc.) can improve the resolution and depth of imaging. Future expansion directions include the development of multimodal imaging techniques suitable for transparent tissues to obtain more information in a single experiment.
Deeper tissue transparency: By developing new and more effective clearing agents, we explore how to achieve clearing effects in deeper tissues (such as the heart, lungs, liver, etc.), thereby improving the non-invasive imaging capabilities of deep organs.
- Author:KCGOD
- URL:https://kcgod.com/make-animal-transparent
- Copyright:All articles in this blog, except for special statements, adopt BY-NC-SA agreement. Please indicate the source!
