College of Engineering Magazine- Fall 2001

Bright Shining Lights

Irving Bigio combines lasers and medicine— and comes up with novel diagnostic tools

by Cynthia K. Buccini

Having a conventional biopsy done today often means facing a scalpel or a needle to remove tissue, then anxiously waiting hours or days to learn if it's cancer or just a scare. Irving Bigio, a new professor in the Departments of Biomedical Engineering and Electrical and Computer Engineering, is working on a better way. Bigio, who joined the staff last February after more than twenty-five years as a scientific staff member at Los Alamos National Laboratory, says the answer lies in biomedical optics - the use of light for diagnostic or therapeutic purposes. Imagine a biopsy that would allow physicians to detect malignancies in the colon, bladder, cervix, or other organs immediately and without removing any tissue, or enable surgeons to determine right away if they've left any cancerous tissue behind.

Bigio is developing such noninvasive diagnostic techniques, called optical biopsy, to identify structural changes in tissue based on its light absorption and scattering properties. It may be years before the optical biopsy is commercially available, but the clinical research shows promise, Bigio says. "The idea here is to be able to provide less invasive diagnostic and therapeutic methods that, hopefully, provide a benefit to the patient at a lower cost to the health care system," he says.

Bigio became interested in biomedical optics at Los Alamos, where he began working in 1974 after receiving a Ph.D. in physics from the University of Michigan. During his first ten years at Los Alamos, his research focused on laser physics and nonlinear optics, but he gradually became interested in medical applications for laser technologies. In the late 1980s, he worked on the development of a nonsurgical laser treatment for enlarged prostates. "We modeled it computationally, built the first prototype instruments, and carried them through animal trials," says Bigio, who received one of the original patents. The technology was approved by the Food and Drug Administration and the device, called the Indigo 830, has been on the market for several years. (Indigo is now a division of Johnson & Johnson.)

Bigio's interest turned from laser therapy applications to noninvasive and minimally invasive diagnostics after receiving a call from a gastroenterologist looking for a better way to detect signs of early cancer. Using an endoscope, the doctor would look inside the colon of a patient suffering from bowel disease and do random biopsies - sending tissue to a lab for examination under a microscope. "They could end up doing thirty or forty biopsies on a patient and still miss the spots of early malignancy because they couldn't see any difference with this normal-illumination endoscope," Bigio says. The physician wanted a "magic laser" he could use with an endoscope that would pinpoint the location of precancerous or cancerous sites and somehow transmit the information to a computer screen. "It turned out his idea wasn't so crazy," Bigio recalls.

The doctor's call led Bigio and his colleagues to develop the optical biopsy method, a technique using a fiber optic probe, which can be passed through an endoscope or catheter and placed in contact with a tissue. The probe's fiber shines white light on, say, the lining of the colon or bladder, and an adjacent optical fiber collects the light that the tissue emits. "The light that comes back is not necessarily the same white spectrum that went in," Bigio says. "If the sizes and densities of the things that scatter light - the nuclei and other cell components - change, that will change the spectrum or the range of colors of light that we get back." The idea is that the cellular components of cancerous tissue are different from those of normal tissue, and therefore will scatter light differently. "You analyze the spectrum to deduce the condition of the tissue," Bigio says. Bigio and his colleagues are still conducting clinical studies on the optical biopsy system, and it could be three or four years before it is commercially available. The initial results look promising, he says. "The system gives us a simple instantaneous optical measurement that we can do on a tissue, which relates fairly directly to what a pathologist deduces when he looks at the tissue under the microscope." Instead of a microscope, however, the biomedical optics system uses a spectrometer, which is connected to the fiber optic probe, and a laptop computer, which displays on its screen the spectrum of light emitted by the tissue.

An Eye on Cancerous Cells

"We've also been doing clinical studies using our method for breast cancer applications, in particular, to develop a tool to assist a surgeon in checking the resection margins when they do a partial mastectomy or lumpectomy, to make sure they didn't leave any cancer behind," Bigio says. The new method would allow surgeons to learn immediately if any cancerous tissue remains. Malignant tissue is often left behind during such procedures - as much as 10 to 40 percent of the time - depending on how aggressive the surgeon is and how much of the breast the woman wants to preserve, Bigio says. More surgery is then required. Bigio is also working on an optical probe that would measure drug concentrations in tissue by looking at the relative absorption of different colors of light in the tissue. The probe would be particularly useful in determining whether there is more of a chemotherapy drug in a patient's tumor than in nearby normal tissue. "If a chemotherapy agent doesn't get into the tumor, then it's not going to treat it," Bigio explains. "Some drugs get into tumors more easily than others and some are rejected by tumors. With an optical technique that's essentially noninvasive, a probe is put up against a tissue you want to measure and it tells you how much of the drug is in the tissue."

The probe would also enhance a new chemotherapy treatment called photodynamic therapy, in which the drug is administered to the patient and is activated later by illuminating it with a specific color of light. "The technique would allow you to know when the dose is right and when the time is right for activating the drug," Bigio says.

Bigio says similar methods may be developed to identify different types of bacteria. He thinks a tool can be developed to help doctors determine what kind of bacterium is causing an infection. "Imagine that you could shine ultraviolet or blue light on a surface where you suspect there is a bacterial species, then spectrally analyze the light," he says. "We've actually done some optical measurements on bacterial species and shown that we can distinguish them to some extent." The technique isn't close to clinical trials, but Bigio says he is building a research program and looking for funding to advance it.

Back to the Classroom

When he arrived at the College of Engineering in February, Bigio set to work developing graduate-level courses - he's teaching Introduction to Biomedical Optics and Biophotonics this fall - and equipping two new laboratories that BU built to his specifications. (He had a lot of buying to do when he arrived in Boston. He and his wife lost everything when their home in Los Alamos burned to the ground in May 2000 in the worst wildfire in New Mexico's history. After they bought their house in Brookline, they had to start from scratch. "Not just furniture," Bigio says, "but sheets and towels, dishes and silverware, scissors and Scotch tape, clothes and the little screwdriver that you fix your eyeglasses with. It's a rebuilding of one's life from all aspects, not just careerwise and socially, but literally all of the day-to-day things in one's life.")

Bigio says he decided to leave Los Alamos for the University because he enjoys teaching, citing his experiences as a Fulbright Scholar at Israel's Weizmann Institute of Science during the 1976-77 academic year and as a visiting professor at the University of Copenhagen during the summers of 1985, 1987, and 1989. He also spent most of the 1994-95 year as a guest fellow at Oxford University's Pembroke College, where he began building clinical collaborations with the Medical School of University College London. He says he was also drawn to the Boston area, with its prominent and respected medical research centers; now he's setting up research collaborations with some, including the Boston University School of Medicine and Harvard University.

College of Engineering Dean David Campbell, who recruited Bigio, has known him since 1975 when the two were neighbors and colleagues at Los Alamos National Laboratory. Campbell followed Bigio's career since then, and when Campbell was appointed dean of the College last year, Bigio was on his short list of high-priority recruits.

Campbell says Bigio's joint appointment will help strengthen the links between the biomedical engineering and computer and electrical engineering departments. And he predicts that Bigio will be an outstanding professor and mentor of students. "He cares passionately about his research, about his field, about making a contribution to medicine, and about his students," Campbell says.


Bright Shining Lights Irving Bigio combines lasers and medicine— and comes up with novel diagnostic tools by Cynthia K. Buccini Having a conventional biopsy done today often means facing a scalpel or a needle to remove tissue, then anxiously waiting hours or days to learn if it's cancer or just a scare. Irving Bigio, a new professor in the Departments of Biomedical Engineering and Electrical and Computer Engineering, is working on a better way. Bigio, who joined the staff last February after more than twenty-five years as a scientific staff member at Los Alamos National Laboratory, says the answer lies in biomedical optics - the use of light for diagnostic or therapeutic purposes. Imagine a biopsy that would allow physicians to detect malignancies in the colon, bladder, cervix, or other organs immediately and without removing any tissue, or enable surgeons to determine right away if they've left any cancerous tissue behind. Bigio is developing such noninvasive diagnostic techniques, called optical biopsy, to identify structural changes in tissue based on its light absorption and scattering properties. It may be years before the optical biopsy is commercially available, but the clinical research shows promise, Bigio says. "The idea here is to be able to provide less invasive diagnostic and therapeutic methods that, hopefully, provide a benefit to the patient at a lower cost to the health care system," he says. Bigio became interested in biomedical optics at Los Alamos, where he began working in 1974 after receiving a Ph.D. in physics from the University of Michigan. During his first ten years at Los Alamos, his research focused on laser physics and nonlinear optics, but he gradually became interested in medical applications for laser technologies. In the late 1980s, he worked on the development of a nonsurgical laser treatment for enlarged prostates. "We modeled it computationally, built the first prototype instruments, and carried them through animal trials," says Bigio, who received one of the original patents. The technology was approved by the Food and Drug Administration and the device, called the Indigo 830, has been on the market for several years. (Indigo is now a division of Johnson & Johnson.) Bigio's interest turned from laser therapy applications to noninvasive and minimally invasive diagnostics after receiving a call from a gastroenterologist looking for a better way to detect signs of early cancer. Using an endoscope, the doctor would look inside the colon of a patient suffering from bowel disease and do random biopsies - sending tissue to a lab for examination under a microscope. "They could end up doing thirty or forty biopsies on a patient and still miss the spots of early malignancy because they couldn't see any difference with this normal-illumination endoscope," Bigio says. The physician wanted a "magic laser" he could use with an endoscope that would pinpoint the location of precancerous or cancerous sites and somehow transmit the information to a computer screen. "It turned out his idea wasn't so crazy," Bigio recalls. The doctor's call led Bigio and his colleagues to develop the optical biopsy method, a technique using a fiber optic probe, which can be passed through an endoscope or catheter and placed in contact with a tissue. The probe's fiber shines white light on, say, the lining of the colon or bladder, and an adjacent optical fiber collects the light that the tissue emits. "The light that comes back is not necessarily the same white spectrum that went in," Bigio says. "If the sizes and densities of the things that scatter light - the nuclei and other cell components - change, that will change the spectrum or the range of colors of light that we get back." The idea is that the cellular components of cancerous tissue are different from those of normal tissue, and therefore will scatter light differently. "You analyze the spectrum to deduce the condition of the tissue," Bigio says. Bigio and his colleagues are still conducting clinical studies on the optical biopsy system, and it could be three or four years before it is commercially available. The initial results look promising, he says. "The system gives us a simple instantaneous optical measurement that we can do on a tissue, which relates fairly directly to what a pathologist deduces when he looks at the tissue under the microscope." Instead of a microscope, however, the biomedical optics system uses a spectrometer, which is connected to the fiber optic probe, and a laptop computer, which displays on its screen the spectrum of light emitted by the tissue. An Eye on Cancerous Cells "We've also been doing clinical studies using our method for breast cancer applications, in particular, to develop a tool to assist a surgeon in checking the resection margins when they do a partial mastectomy or lumpectomy, to make sure they didn't leave any cancer behind," Bigio says. The new method would allow surgeons to learn immediately if any cancerous tissue remains. Malignant tissue is often left behind during such procedures - as much as 10 to 40 percent of the time - depending on how aggressive the surgeon is and how much of the breast the woman wants to preserve, Bigio says. More surgery is then required. Bigio is also working on an optical probe that would measure drug concentrations in tissue by looking at the relative absorption of different colors of light in the tissue. The probe would be particularly useful in determining whether there is more of a chemotherapy drug in a patient's tumor than in nearby normal tissue. "If a chemotherapy agent doesn't get into the tumor, then it's not going to treat it," Bigio explains. "Some drugs get into tumors more easily than others and some are rejected by tumors. With an optical technique that's essentially noninvasive, a probe is put up against a tissue you want to measure and it tells you how much of the drug is in the tissue." The probe would also enhance a new chemotherapy treatment called photodynamic therapy, in which the drug is administered to the patient and is activated later by illuminating it with a specific color of light. "The technique would allow you to know when the dose is right and when the time is right for activating the drug," Bigio says. Bigio says similar methods may be developed to identify different types of bacteria. He thinks a tool can be developed to help doctors determine what kind of bacterium is causing an infection. "Imagine that you could shine ultraviolet or blue light on a surface where you suspect there is a bacterial species, then spectrally analyze the light," he says. "We've actually done some optical measurements on bacterial species and shown that we can distinguish them to some extent." The technique isn't close to clinical trials, but Bigio says he is building a research program and looking for funding to advance it. Back to the Classroom When he arrived at the College of Engineering in February, Bigio set to work developing graduate-level courses - he's teaching Introduction to Biomedical Optics and Biophotonics this fall - and equipping two new laboratories that BU built to his specifications. (He had a lot of buying to do when he arrived in Boston. He and his wife lost everything when their home in Los Alamos burned to the ground in May 2000 in the worst wildfire in New Mexico's history. After they bought their house in Brookline, they had to start from scratch. "Not just furniture," Bigio says, "but sheets and towels, dishes and silverware, scissors and Scotch tape, clothes and the little screwdriver that you fix your eyeglasses with. It's a rebuilding of one's life from all aspects, not just careerwise and socially, but literally all of the day-to-day things in one's life.") Bigio says he decided to leave Los Alamos for the University because he enjoys teaching, citing his experiences as a Fulbright Scholar at Israel's Weizmann Institute of Science during the 1976-77 academic year and as a visiting professor at the University of Copenhagen during the summers of 1985, 1987, and 1989. He also spent most of the 1994-95 year as a guest fellow at Oxford University's Pembroke College, where he began building clinical collaborations with the Medical School of University College London. He says he was also drawn to the Boston area, with its prominent and respected medical research centers; now he's setting up research collaborations with some, including the Boston University School of Medicine and Harvard University. College of Engineering Dean David Campbell, who recruited Bigio, has known him since 1975 when the two were neighbors and colleagues at Los Alamos National Laboratory. Campbell followed Bigio's career since then, and when Campbell was appointed dean of the College last year, Bigio was on his short list of high-priority recruits. Campbell says Bigio's joint appointment will help strengthen the links between the biomedical engineering and computer and electrical engineering departments. And he predicts that Bigio will be an outstanding professor and mentor of students. "He cares passionately about his research, about his field, about making a contribution to medicine, and about his students," Campbell says.
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