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Low-cost imaging system uses fluorescent molecules to determine the depth of tumor cells
Researchers have developed a low-cost, simple imaging system that uses tumor-targeted fluorescent molecules to determine the depth of tumor cells in the body. The portable system could eventually help surgeons more accurately distinguish between healthy and cancerous tissue when removing a tumor. Doctors can use fluorescent molecules during tumor resection to make cancer cells glow, allowing the surgeon to see if cancer tissue is still present. However, the equipment required for this technique is not widely available and typically does not provide quantitative information about how deep the cancer cells are in the tissue. Access to…
Low-cost imaging system uses fluorescent molecules to determine the depth of tumor cells
Researchers have developed a low-cost, simple imaging system that uses tumor-targeted fluorescent molecules to determine the depth of tumor cells in the body. The portable system could eventually help surgeons more accurately distinguish between healthy and cancerous tissue when removing a tumor.
Doctors can use fluorescent molecules during tumor resection to make cancer cells glow, allowing the surgeon to see if cancer tissue is still present. However, the equipment required for this technique is not widely available and typically does not provide quantitative information about how deep the cancer cells are in the tissue. Access to deep information would help surgeons remove a complete layer of healthy tissue around the tumor, which has been proven to provide the best possible results for patients.
The few commercial systems that provide quantitative depth information are large and expensive, limiting use outside of large medical centers. Our group built on previous work in this area to develop a low-cost, simple system that can quickly determine the depth of tumor cells using near-infrared (NIR) fluorescent probes.”
Christine M. O’Brien of the Samuel Achilefu Laboratory at Washington University School of Medicine in St. Louis, leader of the research team
The researchers describe their new system in the Optica Publishing Group journal Biomedical Optics Express. The portable and easy-to-use system could be used in low-resource clinical centers, which could help minimize health disparities.
“Systems like this could be used in the future to improve surgical outcomes for patients undergoing tumor removal,” O’Brien said. “It would also eliminate the need to wait for pathology results before confirming whether cancer cells are still present after tumor removal.”
Making Cancer Shine
Research has shown that surgical treatments for cancer are usually most successful when surgeons remove not only the tumor but also a healthy layer of tissue that completely surrounds it. However, this can be difficult because it is difficult to determine the boundaries between the end of the tumor and the beginning of healthy tissue. In addition, the optimal thickness of the healthy layer depends on the type and location of the tumor.
To support this task, the Achilefu Lab research team led by O’Brien developed a new tool based on the application of a single fluorescent dye during tumor resection, which can then be excited by two different NIR wavelengths that penetrate different depths into the tissue. The emitted NIR fluorescence can be imaged through tissue, allowing detection of cancer cells 1 to 2 centimeters below the surface.
Dual wavelength excitation fluorescence takes advantage of the fact that different colors or wavelengths of light travel different distances within the tissue. By illuminating tumor-targeting fluorescent molecules with different wavelengths of light and comparing their reactions, it is possible to predict how deep the tumor-targeting agents are located in the tissue.
“Several research groups have contributed to the development of mathematical relationships that link fluorophore depth to ratiometric fluorescence measurements,” said O’Brien. “The increasing development of near-infrared contrast agents for use in medicine encouraged us to build on previous work and develop a system that works in the near-infrared range and is also inexpensive and easy to use.”
Building a system with two wavelengths
The new fluorescence imaging system uses 730 nm and 780 nm LEDs to provide the two wavelengths of excitation light and a monochrome CMOS camera to capture the resulting fluorescence. An 850 nm LED was also incorporated to generate a bright field image, allowing correlation of the fluorescence images with the real view of the tissue. The researchers chose to use an experimental agent developed in the Achilefu laboratory called LS301, which can be administered during tumor resection, as a cancer-targeting infrared probe because its broad excitation spectrum eliminates the need to use more than one fluorophore, which would otherwise have made the clinical application more complex. LS301 is currently being tested in clinical trials on breast cancer patients.
After testing the system on layered synthetic materials and chicken slices, the researchers assessed its ability to predict the depth of a tumor using mammary tumors grown in mice. This was done by injecting the mice with LS301 and then imaging them with the system. Capturing the necessary images took 5 minutes. The calculations based on these images correlated well with the actual depth of the tumor and showed an average error of only 0.34 mm, which is probably acceptable for clinical use.
The researchers are now working to make the system even more useful for surgical guidance by speeding up data processing and adding additional automation to the system so that it can scan the entire tissue surface.
Source:
Reference:
O'Brien, CM, et al. (2022) Quantitative tumor depth determination using dual-wavelength excitation fluorescence. Biomedical Optics Express. doi.org/10.1364/BOE.468059.
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