Deep near-IR imaging method could enable earlier cancer detection

The researchers hope to adapt their near-IR imaging technology for early diagnosis of ovarian and other types of cancer.

Content Dam Bow Online Articles 2019 03 Mit Deep Tissue Imaging

A team of researchers at the Massachusetts Institute of Technology (MIT; Cambridge, MA) has developed a near-infrared (near-IR) imaging system that can detect tumors as small as a couple of hundred cells deep within the body.

In a study, the researchers used their near-IR imaging system to track a 0.1 mm fluorescent probe through the digestive tract of a living mouse. They also showed that they can detect a signal to a tissue depth of 8 cm. They hope to adapt their imaging technology for early diagnosis of ovarian and other types of cancer that are currently difficult to detect until late stages.

Existing methods for imaging tumors all have limitations that prevent them from being useful for early cancer diagnosis. Most have a tradeoff between resolution and depth of imaging, and none of the optical imaging techniques can image deeper than about 3 cm into tissue. Commonly used scans such as x-ray computed tomography (CT) and magnetic resonance imaging (MRI) can image through the whole body, but they cannot reliably identify tumors until they reach about 1 cm in size.

Angela Belcher, the James Mason Crafts Professor of Biological Engineering and Materials Science at MIT, a member of the Koch Institute for Integrative Cancer Research, and the newly appointed head of MIT’s Department of Biological Engineering, and her team set out to develop new optical methods for cancer imaging several years ago, when they joined the Koch Institute. They wanted to develop technology that could image very small groups of cells deep within tissue and do so without any kind of radioactive labeling.

Near-infrared light is well suited to tissue imaging because light with longer wavelengths doesn't scatter as much as when it strikes objects, which allows the light to penetrate deeper into the tissue. To take advantage of this, the researchers used an approach known as hyperspectral imaging, which enables simultaneous imaging in multiple wavelengths of light.

Related: Hyperspectral microscopy serves biological pathology

The researchers tested their system with a variety of near-IR fluorescent light-emitting probes, mainly sodium yttrium fluoride nanoparticles that have rare earth elements such as erbium, holmium, or praseodymium added through a process called doping. Depending on the choice of the doping element, each of these particles emits near-infrared fluorescent light of different wavelengths.

Using algorithms that they developed, the researchers can analyze the data from the hyperspectral scan to identify the sources of fluorescent light of different wavelengths, which allows them to determine the location of a particular probe. By further analyzing light from narrower wavelength bands within the entire near-IR spectrum, the researchers can also determine the depth at which a probe is located. The researchers call their system "DOLPHIN," which stands for "Detection of Optically Luminescent Probes using Hyperspectral and diffuse Imaging in Near-infrared."

Content Dam Bow Online Articles 2019 03 Mit Deep Tissue Imaging

MIT researchers have devised a way to simultaneously image in multiple wavelengths of near-infrared light, allowing them to determine the depth of particles emitting different wavelengths. (Image courtesy of the researchers)

To demonstrate the potential usefulness of this system, the researchers tracked a 0.1-mm-sized cluster of fluorescent nanoparticles that was swallowed and then traveled through the digestive tract of a living mouse. These probes could be modified so that they target and fluorescently label specific cancer cells.

The researchers also demonstrated that they could inject fluorescent particles into the body of a mouse or a rat and then image through the entire animal, which requires imaging to a depth of about 4 cm, to determine where the particles ended up. And in tests with human tissue-mimics and animal tissue, they were able to locate the probes to a depth of up to 8 cm, depending on the type of tissue.

This kind of system could be used with any fluorescent probe that emits light in the near-IR spectrum, including some that are already FDA-approved, the researchers say. The team is also working on adapting the imaging system so that it could reveal intrinsic differences in tissue contrast, including signatures of tumor cells, without any kind of fluorescent label.

In ongoing work, they are using a related version of this imaging system to try to detect ovarian tumors at an early stage. Ovarian cancer is usually diagnosed very late because there is no easy way to detect it when the tumors are still small.

"Ovarian cancer is a terrible disease, and it gets diagnosed so late because the symptoms are so nondescript," Belcher says. "We want a way to follow recurrence of the tumors, and eventually a way to find and follow early tumors when they first go down the path to cancer or metastasis. This is one of the first steps along the way in terms of developing this technology."

The researchers have also begun working on adapting this type of imaging to detect other types of cancer such as pancreatic cancer, brain cancer, and melanoma.

Full details of the work appear in the journal Scientific Reports.

More in Cell Biology