Fluorescent quantum dots are valuable tools used to tag and image biological processes in live animals. However, precise fluorescent imaging at the cellular and molecular levels has not been possible because of non-specific fluorescence and light scattering by surrounding tissues. Now researchers have created short wave infrared (SWIR) quantum dots that resolve many of these problems. The system was used in live mice to image working organs, take metabolic measurements, and track microvascular blood flow in normal brain and brain tumors.
“Quantum dots are small (nanoscale) particles that can be engineered to emit light at different wavelengths,” explains Behrouz Shabestari, Ph.D., director of the Optical Imaging Program at NIH’s National Institute of Biomedical Imaging and Bioengineering, which co-funded the research. “When they are injected into a live animal, the emitted fluorescent light can be seen with special cameras. By engineering the dots to bind to specific tissues of interest, researchers can use them to study biological processes in real-time.”
An international group of investigators led by Moungi G. Bawendi, Ph.D., the Lester Wolfe Professor in Chemistry at the Massachusetts Institute of Technology, collaborated to create what Bawendi calls the “next-generation,” of quantum dots.
Said Bawendi, “We took advantage of the special qualities of short wave infrared light, which is essentially the ability to give a clear bright signal emitted from the tissue of interest that is not blocked or scattered by the surrounding tissues. The system allows us to view biological processes in living, moving animals with great clarity and detail.”
The work is described in the April issue of the journal Nature Biomedical Engineering ("Next-generation in vivo optical imaging with short-wave infrared quantum dots").
The top outlines the experimental set-up with composite SWIR quantum dots injected into the circulation and then imaged through a cranial window in the mouse brain. The bottom shows the resulting fluorescent image with healthy arteries in red, veins in blue, and the disorganized blood vessels of a brain tumor in green.
Engineering SWIR quantum dots to target tissues of interest.
The first type of SWIR-QDs were engineered with phospholipid micelle surface coatings. Micelles are small particles that have a hydrophilic (water-loving) outer shell and a hydrophobic (water repelling) inner layer. The micelle-embedded SWIR-QDs dissolved and circulated through the bloodstream for an extended period, allowing the researchers to study heart and respiration rates in awake mice.
The advantage of these SWIR-QDs is the ability to image physiological processes that occur too rapidly to be detected by common imaging methods such as MRI or PET. This ability would allow unobtrusive monitoring of animals in their normal environment for changes in heartbeat and breathing rates during various exercise tests or in response to drug candidates for conditions such as cardiac arrhythmia.
The second type of SWIR-QDs created were embedded in chylomicrons. Chylomicrons are lipoprotein particles that consist of triglycerides, phospholipids, cholesterol, and proteins and are known to transport dietary lipids from the intestines to other locations. These SWIR-QDs were used to study the movement and metabolism of lipids between brown adipose tissue, blood, and liver in real-time. The researchers explained that lipid-coated SWIR-QDs could be used to assess the immediate effects of medications designed to affect lipid metabolismfor example, to increase the liver’s uptake of lipids from the bloodstream of an individual with high cholesterol.
a) Experimental set-up with lipid micelle SWIR quantum dots injected into the circulation and whole body scan with SWIR camera. b) Resulting fluorescent image shows the accumulation of the lipid micelle SWIR quantum dots in the liver (blue circle) and heart (red circle).
These SWIR-QDs would make it possible to measure blood flow in the brain before and after a stroke, and changes in response to experimental stroke medications.
“In addition to the ability to test much-needed new medications to treat stroke, the potential application to difficult-to-treat tumors is one that we are also very excited about,” said Bawendi. “We can potentially use SWIR-QDs to study how the blood flow pattern in a tumor changes over time. We could monitor disease progression or regression in response to drug treatment. This opens a new way to assess experimental treatments for both stroke and brain cancer that have not been possible with other imaging methods.”
National Institute of Biomedical Imaging and Bioengineering. Posted: Jun 06, 2017.