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Photoacoustic technique could advance breast cancer detection

BioPhotonics
Nov 2007
Method uses ultrasound to measure changes resulting from tumor formation

Gary Boas

Breast cancer accounts for the highest number of malignancies among women worldwide — and its incidence is rising, with an estimated 1.4 million new cases to be diagnosed in 2010. Currently, detection and diagnosis of breast cancer rely on x-ray mammography, ultrasound imaging and biopsy. The three techniques provide a high degree of accuracy but suffer various drawbacks. X-ray mammography can miss cancers, especially in radiodense glandular breasts, and patient discomfort and the possible dangers of ionizing radiation are cause for concern. Ultrasound imaging isn’t yet mature enough for large-scale application, and the invasiveness of a biopsy can cause significant patient trauma.

Researchers therefore have sought alternative imaging modalities for detection and diagnosis of breast cancer. Near-infrared optical imaging has gained popularity in recent years because it is relatively inexpensive and requires neither ionizing radiation nor severe breast compression.

The technique takes advantage of the changes in blood oxygenation resulting from the increased metabolic and vascular demands associated with tumor formation; photons are absorbed by oxyhemoglobin, allowing clinicians to reconstruct images of the tumor after detecting those photons that are not absorbed. However, because the photons are strongly scattered in the tissue, the technique offers relatively poor spatial resolution.

In the Sept. 17 issue of Optics Express, a team with the University of Twente and Medisch Spectrum Twente, both in Enschede, and the Academic Medical Center, in Amsterdam, all in the Netherlands, reported the use of a photoacoustic technique for breast imaging.

The investigators’ technique depends on absorbed photons for a signal. Absorption leads to thermalization, producing localized temperature increases and, consequently, thermal expansion at the sites of absorption. When pulses of light are applied, the resulting pressure transients are detectable using conventional ultrasound detectors, which allows measurement of the spatial distribution of the absorbing structures. Because ultrasound scatters considerably less in soft tissue than light does, this imaging technique can offer higher spatial resolution than light-based techniques.

The study was motivated by a desire to validate both the technique and the instrument (dubbed the Twente Photo-acoustic Mammoscope) that the researchers had developed.

“Though results have been shown by Oraevsky’s group at Fairway Medical Systems, the field is as yet fledgling,” said Srirang Manohar, the first author of the study, “and we wanted to develop a knowledge base in the feasibility and limitations of using photoacoustic imaging as embodied in the mammoscope for detecting and/or diagnosing cancer in the breasts of human patients.”

BRAcoustic_Fig-1_PAM.jpg
Researchers have demonstrated a photoacoustic imaging technique for detection and diagnosis of breast cancer. Based on a mammoscope mounted to the frameof a hospital bed, the technique uses ultrasound to detect the absorption of photons transmitted into the breast with higher spatial resolution than is available with light-based methods. Reprinted with permission of Optics Express.

To image patients, the mammoscope is mounted on the frame of a hospital bed. The patient lies on the bed with the breast being imaged suspended through an aperture. Under the bed, it is compressed mildly between the detector matrix, which is made by Lunar Corp., now part of GE Healthcare — with 590 active elements that are activated sequentially — and the glass plate of a compartment with the scanning system in it. Light from a 1064-nm laser made by Quantel SA of Les Ulis, France, mounted at the bottom of the bed is transmitted to the scanning system. The photoacoustic scan is performed by stepping the laser beam across the region of breast that is suspected to have a tumor through the glass plate.

Unlike previous studies using photoacoustics, in which semicircular ultrasound detector arrays were used, the investigators used a flat array. “We believe that, in principle, using a planar geometry will make comparison of photoacoustic findings with x-ray mammograms easier if the entire breast is scanned,” Manohar said.

They tested the technique by imaging patients with a palpable lump in the breast that was suspected of malignancy and comparing the findings with diagnostic x-ray images obtained with the Selenia Full Field Digital Mammography System made by Hologic Inc. of Bedford, Mass., as well as with sonograms acquired with the iU22 ultrasound system made by Philips Medical Systems of Best, the Netherlands. A dedicated breast imaging radiologist interpreted both the mammograms and the sonograms.

The researchers developed a systematic study protocol in which the photoacoustic scan was performed after diagnostic x-ray and sonography but prior to biopsy. “A biopsy could result in hematoma or internal bleeding that could show up in the photoacoustic image since the technique is sensitive to absorption by blood,” Manohar said.

They encountered several challenges during the study. Initially, they had difficulty with women with smaller breasts and in cases in which the tumor was located too close to the chest wall. They redesigned parts of the bed so that they could remove parts of the detector holder when necessary, for example, to get closer to the chest wall during measurements. Manohar noted, though, that these concerns likely will continue for this — indeed for most — breast imaging technique.

The researchers also observed that scanning a large breast area can be time-consuming because the detector is activated element by element. To minimize the time, they imaged only in regions of interest where a tumor was suspected. To this end, it was necessary to position the breast with the help of nursing staff so that the region of interest lay within set scanning coordinates. “This was not easy at the beginning of the study,” Manohar said, “but as the nurses developed experience, it became quite standard.”

BRAcoustic_Fig-2_12mm.jpg
The investigators imaged a region of interest in the breast of a patient with a suspected abnormality. Shown is a slice at a depth of 12 mm from the surface of the breast. The peculiar ring-shaped structure possibly marks the tumor invasion front with increased vascularization. The tumor was diagnosed postsurgically to be malignant.

Despite these challenges, they showed that, in four of the five patients, it revealed higher absorption in regions of interest that were associated with tumor vascularization. In one patient, the method suggested malignancy, whereas the indicators were obscured on the radiological images. The technique’s ability to identify vascular features that the other methods might miss underscores its potential for breast cancer detection and diagnosis.

There is still work to be done, however. To be clinically applicable, Manohar said, the measurement speed should be reduced to under a few minutes, and full-breast scans should be possible regardless of breast size. They are working to address these challenges and are seeking to incorporate quantitative spectroscopic imaging to study the concentrations of hemoglobin, oxygen saturation and other parameters, which will assist diagnosis, according to Manohar.


GLOSSARY
ionizing radiation
Generally, any radiation that can form ions, either directly or indirectly, while traveling through a substance.
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