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“With laser light you are amplifying the number of photons that make up light but only in one particular direction and only in one particular color. So you have highly focused optical energy.” (Photo by Justin Knight)
Mastering the “Light Touch”
For Sergio Fantini, lasers can illuminate our understanding and care of the body

The word laser has such common currency today that few probably realize it started out as an acronym: Light Amplification by Stimulated Emission of Radiation. Invented in 1958 by A. L. Schawlow and C. H. Townes, it was first considered a toy for physicists. Today, from the proverbial laser gun of science fiction movies to more controversial scenarios, lasers continue to provoke the imagination. At Tufts, the applications are based solidly in resolving complex problems and diagnostic challenges confronted in medical care. In the newly established Department of Biomedical Engineering, Assistant Professor Sergio Fantini explores that frontier of therapeutic and diagnostic tools—how light emitted by lasers can be used to cure diseases and to look inside the body to identify potential medical problems. A native of Italy, educated in Florence, and trained as a physicist, he brings an inventive approach to this emerging field. He holds several patents, including one for optical mammography, which offers a new approach to the imaging of breast tumors.

What is the basic principle of lasers?
There are unique features of laser light that cannot be found in nature. Laser light has one single color; it’s monochromatic. It moves in only one direction; it’s not diffuse. With laser light you are amplifying the number of photons that make up light but only in one particular direction and only in one particular color. So you have highly focused optical energy. If you turn on a 50-watt lightbulb you can be sure that you are safe, but if you had a 50-watt laser beam it would drill a hole in your skin.

What are the benefits of lasers?
The main advantage of a laser-based instrument for medical diagnostics is practical: it’s inexpensive, it may be packaged into portable units and the light is perfectly safe. Also, it can be applied noninvasively. It’s not painful and there are no probes under the skin.

How does the light actually illuminate?
We use red and near-infrared light, which penetrates deeply into tissue; blue and green light will not. When you hold a flashlight up to your hand, you see that red comes out; red is not being absorbed because water and blood, two of the main tissue constituents, are relatively transparent to red light. The basic idea is that this light, once it is in the tissue, is affected by the presence of hemoglobin, a protein in the blood responsible for oxygen transportation. The color of blood is different depending on its level of oxygenation: red blood indicates it’s richly oxygenated. The key aspect here is that we will see a difference in light transmission as oxygen is exchanged from the blood to the tissue, thus obtaining a measure of the balance between the oxygen supply and the oxygen consumption, which is an indicator of the tissue viability.

So X rays look at density of tissue but laser light is looking at a metabolic process.
Right, the process of oxygenation. Blood changes in color as it becomes deoxygenated on its course through the body. In your veins, for instance, where there is lower oxygenation than in the arteries, the color of the blood appears blue. When you cut yourself, the blood that comes out picks up oxygen from the air and turns red.

What drew you to the field of lasers?
I still remember a conversation that I had many years ago with a salesperson who told me that a CD player uses laser light, which, he said, “is essentially like confining all the light in this room to a small point.” I was fascinated by the idea, but I thought that there must have been a more rigorous explanation of laser light. As a result, as a physics student, I was attracted by the physics of lasers, which is based on a number of elegant principles. Then, I was interested in the applications of lasers in spectroscopy, and I used a laser to study a new kind of superconductor. When I moved to the University of Illinois at Urbana-Champaign in 1993, I started working on medical applications of lasers, which I felt, and still feel, have a truly outstanding potential and significant societal importance.

What specifically are you doing at Tufts?
I am involved with medical optics, which is using light to collect diagnostic information with a potential for medical applications, just as X rays gather information by using radiation. The practical difference is that X rays are an ionizing radiation; the energy applied is sufficient to separate the electrons from the atoms and molecules. When this phenomenon affects water, a major component of most living tissues, it results in the production of free radicals, which in turn may induce harmful chemical modifications in organic molecules. This introduces risk or the potential for cancer.

More specifically, we are developing imaging techniques in three areas. We study blood flow and oxygen metabolism of muscles so we can look at the effect of exercise. We have found significant differences between the response to exercise in normal subjects and in patients affected by vascular diseases.

In the case of optical mammography, we know that breast cancer is usually associated with a high concentration of blood vessels and with high metabolic rate. We are trying to take advantage of these features to develop an optical imaging technique that uses this process to tell us more subtle information about what is going on. X-ray mammography, the gold standard today, is very effective in detecting the presence of cancer, but is ineffective in discriminating cancer from other benign tumors. As a result, many women without cancer have a biopsy and endure the emotional reaction to being told that they have a suspicious mass in their breast. So this is the main aspect that can be improved. While more research is needed to identify the potential clinical role of optical mammography, its sensitivity to the oxygenation level of breast tumors may add significant physiological information to the structural information provided by X-ray mammography. With lasers we could determine more precisely the nature of the tumor or mass.

We are also looking at blood-flow changes that are associated with brain activity. Of course, brain activation is an electrical signal, but we would like to understand better the coupling between that electrical activity and the blood-flow response to it, or neurovascular coupling. Today there are a number of techniques that look at blood-flow changes (for instance, functional magnetic resonance imaging) and other techniques, such as EEGs, are sensitive only to electrical signals. There are now reports that optical methods, in addition to being sensitive to blood-flow changes, are sensitive also to electrical signals. If this is confirmed, this feature would render optical imaging of the brain an ideal technology for the study of neurovascular coupling.

What are your long-range goals?
My goal is to introduce some of these optical techniques in hospitals. That’s why it’s so important to have collaborations with physicians who can contribute to research and who understand that this technology may fill some gaps in clinical practice. In optical mammography the gap is clear: there is a lack of specificity for mammograms. I’m also interested in the oxygenation of muscles. Dr. Ronenn Roubenoff, a medical doctor with whom I have collaborated at the New England Medical Center, referred to a number of muscle disorders that are associated with areas of restricted blood flow and currently the only way to identify the problem areas is with a biopsy. But there is no precise guide for where to stick the needle. It would be great to develop and refine this clinical application.

Your office wall is dominated by a facsimile of Raphael’s “School of Athens.” Do you ever wonder what Plato or Aristotle would make of your work?
Not really. But there is one thing in that painting that reminds me of the evolution of my scientific career. Plato points up towards the world of ideas, while Aristotle—who was Plato’s pupil—keeps his right hand down to indicate the world of experience. This reminds me of my own intellectual development—from physics, where I studied basic processes in nature, to biomedical engineering, where I try to use scientific knowledge to realize practical devices for everyday life applications.