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Research gets under the skin

By Steven Schultz

Princeton NJ -- For physics major Anthony Miller, the experience of writing a senior thesis has been everything it is supposed to be. He worked closely with a faculty member, developed an idea and grappled with major intellectual challenges in bringing it to fruition. Along the way, he gained the kind of appreciation for his field that only independent work outside the classroom can bring.

Anthony Miller

Anthony Miller holds a sample of water and dye that substituted for human tissue in his senior thesis research, which explored the use of lasers to create detailed images of the inside of the body. The method could detect tiny tumors or track brain activity.


It also had a bonus: Miller's research is helping scientists create new methods for detecting cancer and studying the brain.

Miller is investigating an idea for using ultrafast pulses of light to probe beneath the surface of the body and produce detailed images of certain tissues and cells. Although his major is physics, he is bridging disciplines by working in the lab of Warren Warren, the Ralph Dornte Professor in Chemistry. Miller's work is a key part of Warren's imaging projects in his labs at Princeton and the University of Pennsylvania, where he is an adjunct professor of radiology.

"Anthony is an exceedingly bright young man," said Warren, "and is working on a conceptually very challenging project to dramatically improve our ability to see into tissue and diagnose disease."

Miller became interested in this research during his sophomore year when he took two of Warren's courses, including a graduate-level seminar on "The Chemistry and Physics of Molecular Imaging." Miller was ahead of schedule in his major because he had taken two semesters of introductory physics at Princeton while still a senior in high school in Hopewell, N.J. By the spring of his sophomore year, Miller was working with Warren on his first junior paper, exploring ideas for quantum computing, a potential approach to making more powerful computers.

"The thing I really liked about Professor Warren's classes was that I was able to see why what I was learning was relevant," said Miller. "When you can relate to the material and understand how it's applicable to the real world, you get so much more out of the class because you are always thinking, 'What does this mean? What can I do with this?'"

Miller went on to try his hand at theoretical physics with a second junior paper on string theory. He also did other experimental work one summer at the University of California-San Diego. His experience working with Warren stayed with him and evolved into a thesis plan.

"The senior thesis is one of the reasons I came to Princeton," Miller said. "I felt that getting to be involved in research was really important. It is different from anything you do in the classroom, a completely different mode of thinking and working."

Miller's thesis research takes advantage of the fact that human flesh, while relatively opaque to visible light, is transparent to infrared light to a depth of about four inches. But shining infrared light on the body results in a fuzzy image because tissue scatters the light. To get around the problem, researchers in Warren's lab are using ultrafast pulses of light (a tenth of a trillionth of a second long), which have very high peak intensity but do not damage the tissue.

Miller's work is helping to show that this technique could detect the pigment melanin in skin and hemoglobin in blood with a microscopic resolution. Producing such a detailed image in deep tissue would be revolutionary, said Warren. Melanin found beneath the surface of the skin can indicate the presence of melanoma. Hemoglobin in blood could be used to track blood flow in the brain, allowing scientists to see what parts of the brain produce different thoughts and behaviors.

Achieving such results requires painstaking "shaping" of these ultrafast laser pulses (rapidly altering their timing and the spectrum of wavelengths they contain). Even with the best control, the signal that bounces back from tissue would be very weak -- just about one light particle out of a million would carry useful information.

"It's been a real learning experience," said Miller, whose work has included both theoretical calculations and experiments. "I expected, pretty naively, that I would be able to come in and begin taking data. [But] it's been months and I've been working in more and more detail as I realize what I have to fix and get perfectly aligned at each stage as [the results] slowly get better."

While Miller is drawn to the fundamental questions behind his work, he also is sustained by the thought of where the research might lead. "I really appreciate the fact that I am doing something that might have medical applications," he said. "It would be amazing if it works and, if all our dreams panned out, we could make real advances in understanding the function of the mind or allow the detection of certain kinds of cancer."

Miller, who also plays the French horn in the University Orchestra and has chaired committees for the model United Nations program, recently won a five-year graduate fellowship from the Hertz Foundation. He is choosing between programs in physics at the California Institute of Technology, Harvard, the Massachusetts Institute of Technology and Stanford.