Biology

Visualizing the Intricacies of Living Tissue with Lasers and Radiation

www.deerfieldfocalpoint.com/articles/visualizing-the-intricacies-of-living-tissue-with-lasers-and-radiation

I. Introduction

With non-invasive imaging methods such as specialized, high-powered lasers and Positron Emission Tomography (PET), researchers are now able to visualize the complexities of living tissue more distinctly without damaging any tissue. As researchers analyze aspects of both PET and newer laser methods, they can determine the effects, limitations and benefits of different techniques to display complex biological systems. Non-invasive methods of studying living tissue are immensely beneficial for biologists due to their ability to detect disease early on and demonstrate cellular function and structure. Additionally, visualizing living tissue is critical for understanding immune diseases, tissue engineering, and drug research.

II. High-Powered Lasers

A new non-invasive imaging method developed by researchers at the Massachusetts Institute of Technology in 2024 can penetrate deeper into living tissue and visualize its intrinsic molecules (Figure 1). Typically, biologists use metabolic imaging, a non-invasive technique, to study living tissue with laser light. However, light scatters when shined into living tissue, causing lower resolution. In recent months, researchers have developed a new method to visualize living tissue more deeply without preprocessing it.

A crucial aspect of this new method is the specific tailoring of the laser’s light to penetrate deeper into tissues. By using a fiber shaper to adjust color and pulses of light, the spread of light is mitigated, which allows researchers to see farther into the tissue and obtain higher resolution images. While testing their method, researchers noticed that the light penetrated over 700 micrometers into the sample tissue as opposed to previous methods that could only reach 200 micrometers.

Two microscopy images side by side, one in grayscale and one in blue, of circular tissue structures
FIGURE 1: LASER LIGHT CAN PENETRATE DEEPER INTO LIVING TISSUE LIU, K., ET AL. (2024). DEEP AND DYNAMIC METABOLIC AND STRUCTURAL IMAGING IN LIVING TISSUES. SCIENCE ADVANCES, 10(50). HTTPS://DOI.ORG/10.1126/SCIADV.ADP2438
Microscopy image of tissue with green, red and blue stained regions
FARBER, D. L. (2021). TISSUES, NOT BLOOD, ARE WHERE IMMUNE CELLS FUNCTION. NATURE, 593(7860), 506–509. HTTPS://DOI.ORG/10.1038/D41586-021-01396-Y

However, it is difficult to view such intrinsic developments without killing the sample by cutting or staining it. This challenge arises from the fact that researchers monitor the metabolic dynamics within the living tissue while it is still growing. Sixian You, a senior author of a paper on this imaging technique, expresses that “by enabling multimodal metabolic imaging that reaches deeper into tissues, we’re providing scientists with an unprecedented ability to observe nontransparent biological systems in their natural state.” This research could lead to further research critical for the advancement in tissue engineering and drug development because it allows researchers to noninvasively observe living tissue without destroying it.

III. PET Applications

Positron Emission Tomography (PET) models metabolic dynamics using radioactive substances that can display the functions within tissues. In an experiment in 2015, researchers used PET to track immune responses. They first developed a method to site-specifically label a type of antibody fragment (VHH) used for research that contained elements of Fluorine-18. The simplest way for 18F labeling of VHHs was through a two-step process that requires click reactions and a sortase-catalyzed modification. The 18F radionuclide binded to the VHHs through the Diels-Alder reaction, which is a significantly efficient reaction. After the 18F labeled VHH was purified through size-exclusion chromatography, the solution was ready for injection. The VHHs were then used to determine the feasibility of visualizing inflammation in different tumor models. Typically in tumor models, there is a presence of macrophages, which are used to determine if inflammation could be detected. When macrophages are activated, they express classes CD11b and the 18F-VHH7 imaging detected CD11b+ cells, confirming the presence of a tumor as exhibited in Figure 2.

Histogram plots labeled CD11c+CD11b+ and CD11c-CD11b+ for tumors at 6 days and 20 days with an arrow labeled VHH7
FIGURE 2: DETECTION OF CD11B+ CELLS IN MACROPHAGES SULEA T. (2022). HUMANIZATION OF CAMELID SINGLE-DOMAIN ANTIBODIES. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.), 2446, 299–312.

While the inherent immunogenicity of VHHs could hinder their utilization, there could be ways to humanize VHHs such as structural binding modes or resurfacing. Regardless, this confirmation can be a stepping stone for further research with new methods with lasers, as discussed above, and the study of immunobiology.

IIII. Conclusion

By focusing on research regarding two different imaging techniques, a familiar method known as PET and a new method using lasers, researchers are able to analyze the potential improvements and importance of both methods. Biologists are able to examine the correlations and discrepancies between different methods, which will ultimately set the scene for further advancements in immunology, cancer research, tissue engineering, and drug discovery.

Notes

  1. Low, J. C. M., et. al., (2023, February 10). Metabolic Imaging With Deuterium Labeled Substrates. Progress in Nuclear Magnetic Resonance Spectroscopy. https://www.sciencedirect.com/science/article/pii/S007965652300002X Back
  2. Thomas, L. (2022, September 29). What Is The Role of Non-Invasive Imaging In Diagnostics?. News Medical. https://www.news-medical.net/health/What-is-the-Role-of-Non-invasive-Imaging-in-Diagnostics.aspx Back
  3. Traian, S. (2022). Humanization of Camelid Single-Domain Antibodies. Methods in Molecular Biology (Clifton, N.J.). https://pubmed.ncbi.nlm.nih.gov/35157279/ Back
  4. Rashidian, M, et. al., (2015). Noninvasive Imaging of Immune Responses. PNAS. https://www.pnas.org/doi/10.1073/pnas.1502609112 Back
  5. Zewe, Adam. (2024, December 11). Noninvasive Imaging Method Can Penetrate Deeper Into Living Tissue. MIT News | Massachusetts Institute of Technology. https://news.mit.edu/2024/noninvasive-imaging-method-can-penetrate-deeper-living-tissue-1211 Back

Hayden Rector ’25