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Tracking cancer with light and sound

BioPhotonics
Sep 2008
Hank Hogan

Treating tumors with a laser is a hot topic, one that keenly interests Dr. William M. Whelan, associate professor of physics at the University of Prince Edward Island in Charlottetown, Canada. Potentially, lasers can heat up and destroy the cancer in place. The challenge has been how to track the effect of this and other treatments in animals and people. In the past, researchers had to make do with techniques based on ionizing x-rays, which themselves can cause cancer. That fact limited possible imaging

Whelan, Canada research chairman in biomedical optics at the university, now is working with Seno Medical Instruments Inc. of San Antonio on a different approach, one that uses a laser interacting with tissue to generate sound. Such opto-acoustic techniques could solve the imaging problem, Whelan said. “Using light and sound versus ionizing radiation, there is the potential to do imaging more often in terms of looking at a tumor’s response to therapy.”

To avoid ionizing radiation, Whelan and others in the research group he leads used custom-developed fiber-based optical sensors embedded in tissue to monitor optical characteristics of the tissue, primarily looking at the wavelength-dependent scattering coefficient. Heating the tissue with an infrared laser operating in the 8- to 10-μm range caused as much as a fourfold rise in the scattering coefficient. The before-and-after difference measured the response to treatment.

A disadvantage of the approach is that it provides information from only one point. If the investigators wanted to observe another location, the sensor had to be moved to interrogate that spot. Development of the sensor had been under way for several years, but limitations of the technique eventually proved too great.

“We got to a point where we needed more volumetric information in terms of how the treatment is progressing. Opto-acoustics is a good potential solution for this,” Whelan said.

Sound pulse

In opto-acoustics, a pulsed laser shines on tissue. Light at the right wavelength is preferentially absorbed within the tissue, generating a sound pulse at specific locations. An acoustic transducer array outside the body picks up the sound, providing a map of the differential optical absorption in the tissue at specific wavelengths.

Tumors are engorged with blood because of blood vessel growth, or angiogenesis, enabling a system that detects angiogenesis to pinpoint the location of cancer. For opto-acoustic imaging of tumors, 757- and 1064-nm wavelengths are of particular importance. The first is preferentially absorbed by deoxygenated hemoglobin and the second, by oxygenated hemoglobin. Thus, with two lasers, an opto-acoustic system can provide not only structural but also functional information.

As a bonus, research has shown that therapeutic heating can cause increased optical absorption and greater stiffness of tissue. These changes affect the opto-acoustic signal generation, as does the intensity of the light. Consequently, tumors treated by laser heating could be particularly susceptible to opto-acoustic imaging.

TS.jpg
William M. Whelan and student Michelle MacPhee use the opto-acoustic small-animal imaging device in Whelan's lab at the University of Prince Edward Island in Charlottetown, Canada.

In using Seno’s opto-acoustic system, Whelan is working with one of the company’s two product lines — the one intended for cancer researchers and designed to image small animals. The other line is aimed at clinical use in breast cancer. The two lines have much in common, with the exception of the probe design and some differences resulting from the nature of the imaging subject, said Seno Chairman and CEO Janet Campbell. “The research device is designed to work on nude mice and uses water as the coupling agent, while we will use a specific gel designed for opto-acoustics on humans.”

Whole-body imaging

Another difference, she added, is that the instrument views the entire body. The clinical device, on the other hand, will focus only on imaging a specific organ.

She noted that no contrast agents are used and no special facility housing is needed. She also pointed out that the technique could be used for the detection of inflammatory and cardiovascular diseases, as well as stroke. Finally, the ability to do functional imaging without compromising the animal is of particular usefulness in a research setting because it allows longitudinal, or time-dependent, studies.

Whelan noted that the first clinical application of the new imaging system will focus on prostate cancer. The system should allow the researchers to map the effect of thermal therapies. Although the opto-acoustic imager is up and running, he noted that it likely will be next year before data from the first animal studies is published.

Initially, the investigators will look only at the relative change within an animal because they lack a crucial bit of information: They don’t know the fluence, or amount of light, within the tissue at specific points and so cannot determine an absolute scale for the opto-acoustic signal. However, Whelan said that the team eventually will be able to model the fluence distribution, enabling quantitative measurements and comparing one subject with another.

That lies in the future, after further research and development of the technology and techniques. For now, Whelan is happy with the technology’s potential. “I’m very encouraged by the image resolution. You can visualize thermal damage through a couple of centimeters of tissue.”

Contact: William M Whelan, University of Prince Edward Island; e-mail: wwhelan@upei.ca; Barbara Lind, Seno Medical Instruments Inc.; e-mail: blind@senomedical.com.


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