Fluorescence imaging is widely used for visualizing biological tissues such as the back of the eye, where signs of macular degeneration can be detected. It is also commonly used to image blood vessels during reconstructive surgery, allowing surgeons to make sure the vessels are properly connected.
For these procedures, as well as others now in clinical trials, such as imaging tumors, researchers use a portion of the light spectrum known as the near-infrared (NIR) -- 700 to 900 nanometers, just beyond what the human eye can detect. A dye that fluoresces at this wavelength is administered to the body or tissue and then imaged using a specialized camera. Researchers have shown that light with wavelengths greater than 1,000 nanometers, known as short-wave infrared (SWIR), offers much clearer images than NIR, but there are no FDA-approved fluorescence dyes with peak emission in the SWIR range.
“我们发现的是that this dye, which has been approved since 1959, is really the best, the brightest fluorophore that we know of at this point for imaging in the short-wave infrared," says Moungi Bawendi, the Lester Wolf Professor of Chemistry at MIT. "Now clinicians can start to try short-wave imaging for their applications because they already have a fluorophore which is approved for use in humans."
Imaging this dye with a camera that detects short-wave infrared light could allow doctors and researchers to obtain much better images of blood vessels and other body tissues for diagnosis and research.
Bawendi and former MIT research scientist Oliver Bruns are the senior authors of the study, which appears in theProceedings of the National Academy of Sciences. The paper's lead authors are MIT graduate students Jessica Carr and Daniel Franke.
Cutting through the fog
The dye that the researchers used in this study, known as indocyanine green (ICG), fluoresces most strongly around 800 nanometers, which falls within the near-infrared range. When injected into the body, it travels through the bloodstream, making it ideal for angiography (the visualization of blood flowing through vessels). Some robot-assisted surgical systems have incorporated NIR fluorescence imaging to help visualize blood vessels and other anatomical features.
Bawendi's lab and other researchers have been interested in developing fluorophores for SWIR imaging because SWIR offers better contrast and clarity than NIR. Light with shorter wavelengths tends to scatter off of imperfections in objects that it strikes, but as wavelengths become longer, scattering is greatly reduced.
Short-wave infrared can also penetrate deeper into tissue, although calculating exactly how far is a complicated process, the researchers say, because it depends on the size of the structure being viewed and the field of view of the microscope. In the new study, the researchers were able to see several hundred micrometers into tissue using a regular fluorescence microscope. Normally, this depth can be reached only with two-photon microscopy, a much more complicated and expensive type of imaging.
"We found that short-wave infrared is particularly useful for imaging small objects that are on top of a large background, so when you want to do angiography of small vessels, or capillaries, that's significantly easier in the short-wave infrared than in the near-infrared," Franke says.
The researchers also tested another dye that works in the near-infrared. This dye, called IRDye 800CW, is similar to ICG and can be attached to antibodies that target proteins such as those found on tumors. They found that IRDye 800CW also fluoresces brightly in the shortwave-infrared light, thought not as brightly as ICG, and showed that they could use it to image a cancerous tumor in the brains of mice.
To do shortwave-infrared imaging, research labs and hospitals would need to switch from the silicon cameras now used for NIR imaging to an indium gallium arsenide (InGaAs) camera. Until recently, these cameras have been prohibitively expensive, but the prices have been coming down in the past several years.
The research was funded by the National Institutes of Health through the Laser Biomedical Research Center; MIT through the Institute for Soldier Nanotechnologies; the National Science Foundation; and the Department of Energy Office of Science.
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