Novel Technology For Detection of Tiny Tumors By MIT Researchers
Various kinds of cancer could be more easily treated when they had been detected at an earlier stage. MIT researchers have now developed an imaging program, called “DOLPHIN,” which could enable them to locate miniature tumors, as small as a few cells, deep inside the body.
In a new study, the investigators used their imaging program, which is based on near-infrared light, to track a 0.1-millimeter fluorescent probe through the digestive tract of a living mouse. They also revealed that they can detect a signal to a tissue depth of 8 centimeters, much deeper than any present biomedical optical imaging procedure.
The researchers hope to accommodate their imaging technology for early diagnosis of ovarian and other cancers that are presently difficult to discover until later phases.
Lead authors of this research study are – Xiangnan Dang, a former MIT postdoc, also Neelkanth Bardhan, a Mazumdar-Shaw International Oncology Fellow. Jifa Qi and Ngozi Eze, former postdoc Li Gu, postdoc Ching-Wei Lin, graduate student Swati Kataria, along with Paula Hammond, the David H. Koch Professor of Engineering, head of MIT’s Department of Chemical Engineering, and a part of the Koch Institute were also a part of the team.
Current techniques for imaging have limitations that prevent them from being useful for early cancer diagnosis. Most have a tradeoff between depth and resolution of imaging, and not one of the optical imaging methods can picture deeper compared to about 3 centimeters to tissue.
Belcher’s laboratory set out to develop new optical methods for cancer imaging several decades back when they joined the Koch Institute. They wanted to create technology that could image very tiny collections of cells deep inside tissue and do this with no kind of radioactive labeling.
Near-infrared mild, which has wavelengths from 900 to 1700 nanometers, is well-suited to tissue imaging since light with longer wavelengths does not scatter up to when it strikes objects, which allows the light to penetrate deeper into the tissue. To make the most of this, the researchers used an approach known as hyperspectral imaging, which allows simultaneous imaging in multiple wavelengths of light.
The researchers tested their system with an assortment of near-infrared fluorescent light-emitting probes, chiefly sodium yttrium fluoride nanoparticles which have rare earth elements such as erbium, holmium, or praseodymium inserted through a process called doping. Based upon the option of the doping element, each of those particles elicits near-infrared fluorescent light of different wavelengths.
Using algorithms that they created, the researchers can analyze the data in the hyperspectral scanning to identify the sources of fluorescent light of various wavelengths, which permits them to ascertain the location of a particular probe. Researchers also determined the depth at which a probe is situated, by further analyzing light from narrower wavelength bands inside the entire near-IR spectrum. The researchers call their method “DOLPHIN”, which stands for “Detection of Optically Luminescent Probes with Hyperspectral and diffuse Imaging at Near-infrared.”
To illustrate the potential usefulness of the system, the researchers tracked a 0.1-millimeter-sized bunch of fluorescent nanoparticles which was swallowed and then traveled via the digestive tract of a mouse. All these probes could be altered so that they aim and fluorescently label-specific cancer cells.
“In relation to technical applications, this technique would allow us to non-invasively track a 0.1-mm-sized fluorescently-labeled tumor, which is a cluster of about a few hundred cells. To our knowledge, nobody has managed to do this previously using optical imaging techniques,” Bardhan says.
The researchers also demonstrated they could inject Atomic particles into the body of a mouse or a rat and then image during the entire animal, which requires imaging to a depth of approximately 4 centimeters, to determine in which the particles stopped up. And in tests with human tissue-mimics and animal tissue, they could locate the probes to a thickness of around 2 centimeters, depending on the type of tissue.
Guosong Hong, an assistant professor of materials science and technology at Stanford University, explained the new method as “game-changing.”
“This is really amazing work,” says Hong, who was not involved in the research. “For the first time, fluorescent imaging has approached the penetration depth of CT and MRI, while maintaining its naturally high resolution, which makes it appropriate to scan the entire body.”
This kind of system could be employed with almost any fluorescent probe that emits light in the near-infrared spectrum, including some that are already FDA-approved, the investigators say. The researchers are also working on adapting the imaging system so it could show intrinsic differences in tissue comparison, including signatures of tumor cells, without any kind of fluorescent tag.
In continuing work, they are using a related version of this imaging system to attempt and detect ovarian tumors at an early stage. Ovarian cancer is usually diagnosed very late because there’s absolutely no simple method to detect it when the tumors remain tiny.
“Ovarian cancer is a deadly disease, and it gets diagnosed so late because the signs are so nondescript,” Belcher says. “We need the means to follow signals of these microbes, and a means to discover and follow early tumors when they first return the road to cancer or metastasis. This is one of the first steps on the way in terms of developing this technology”
The researchers also have started working on adapting this type of imaging to detect different kinds of cancer such as pancreatic cancer, brain cancer, and melanoma.