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For other articles and previous issues click here. December 16, 2005 New
Light — Optical Imaging Pairs Infrared Light With Ultrasound
to Aid Breast Canceer Diagnosis Although only 10% to 30% of approximately 1.6 million breast biopsies performed each year in the United States result in malignant findings, the rest raise many fears and emotions among patients and their families. Researchers are always looking for noninvasive ways to confirm that a suspicious area on a mammogram is not breast cancer. One of several techniques showing promise for reducing the need for biopsies is optical tomography, which uses near-infrared (NIR) photons for imaging body parts. When combined with standard ultrasound, optical tomography can help physicians quantitatively distinguish early-stage breast cancers from noncancerous lesions, according to Quing Zhu, PhD, associate professor of electrical and computer engineering at the University of Connecticut in Storrs and lead author of a study on its use in breast cancer that appeared in the October issue of Radiology. When a suspicious breast lesion is detected by mammography, ultrasound is often used for further evaluation of the area. Unfortunately, the results from ultrasound alone are not always conclusive enough to avoid a biopsy; some tissue from the suspicious area still must be surgically removed and examined to confirm the diagnosis. Reducing
Biopsies As light passes through the body, a portion of it is absorbed by blood vessels. Optical tomography is based on the idea that this absorbed portion can be quantified by using the reflected or transmitted light received at the body surface. Therefore, it provides clues about the blood vessels through which it has passed, Zhu explains. Optical tomography uses diffused light in the NIR spectrum (700 to 900 nanometers.) “At this spectrum window, light absorption of water is low and light can penetrate deep into biological tissues of several centimeters,” Zhu says. Researchers know that breast cancers have higher microvessel density or higher blood volumes than nonmalignant tissue because of angiogenesis—a key process for tumor growth and metastasis. “Tumor blood volume and microvascular are parameters anatomically and functionally associated with tumor angiogenesis,” Zhu explains. Tumorous and normal blood vessels can be measured using a single optical wavelength. If two or more wavelengths are used, the oxyhemoglobin and deoxyhemoglobin concentrations can be measured and the total hemoglobin concentration can be calculated, Zhu says. The total hemoglobin concentration is directly related to tumor microvessel density, which is known to be highly correlated with malignancy. Hemoglobin
Concentration In another study published in Neoplasia Press in March, the University of Connecticut researchers and physicians found that optical imaging of breast tissue was useful in the assessment of tumor response to treatment in the neoadjuvant setting. The study that appeared in the September/October Radiology was conducted with patients from the Hartford Hospital who were initially referred for ultrasound-guided biopsies from May 2003 to March 2004. Patients with lesions not visible on the ultrasound were not studied. The reported study involved 65 patients who ranged in age from 24 to 80; the mean age was 51; 81 breast lesions were identified among the women. Each patient was examined with ultrasound and optical tomography. Afterward, a biopsy was performed on each breast lesion. Biopsies were performed at multiple locations, including the lesion site, a normal symmetric region of the affected breast, and a normal region of the opposite breast in the same quadrant as the lesion. Normal areas were used as reference. The biopsy results confirmed that eight of the lesions were early-stage invasive carcinomas and 73 lesions were benign. The benign group consisted of 20 fibroadenomas, 15 cases of fibrocystic change, eight cases of fibrosis, eight other solid benign lesions, 21 complex cysts, and one case of hyperplasia, according to the study. Combined
Probe “Because the handheld probe could be easily rotated or translated, at least three coregistered ultrasound and near-infrared data sets were acquired at each location, including the lesion and normal areas,” Zhu says. However, it only took approximately 3 to 4 seconds to acquire the necessary data from each patient. The images and optical data that were collected were then analyzed using a computer algorithm. No significant differences were found among averages in the benign groups, Zhu says, “but both the mean maximum and mean average total hemoglobin levels were significantly higher in the malignant group compared with the mean values of benign groups.” Combining the two techniques is key to its accuracy, Zhu says. “While ultrasound is used to locate the lesion, optical tomography is used to calculate the blood volume in the lesion.” The researchers also compared optical tomography with color Doppler ultrasound and found optical tomography to have significantly higher sensitivity and specificity. Although color Doppler showed blood flow in five of the eight malignant lesions, it also showed blood flow in 20% to 50% of the benign lesions, Zhu says. Clinical
Limitations The problem with small breasts is that probe-to-tissue contact is poor and breast tissue chest-wall conjunction distorts the light propagation. However, she says, the problem could probably be overcome by developing a better light propagation model in layered medium and by improving hardware and probe designs. “It is not a fundamental limitation, but it is a problem that we’re working on.” Darker nipples can present a problem because the light absorption of dark skin is high. “You are looking for cancer, but then the nipple will show up as artifacts,” Zhu explains. The solution, Zhu says, may be a simple matter of pushing the nipple outside the probe. “When you put the probe on top of the dark nipple it’s a problem, but if you can move it around the nipple by positioning the patient and the probe, it’s not.” The technique also poses numerous atmospheric challenges. The optical instruments require good signal-to-noise performance, and the background light must be controlled to limit background interference. “Certain measurement procedures have to be followed to minimize any possible sources that may cause imaging artifacts,” Zhu says. Not only is performing the optical imaging tricky, but so is performing the ultrasound, Zhu says. “Ultrasound has this problem that it is very operator dependent. If you are not careful, you can create false lesions or miss true lesions. Some cases are very easy to see, but others are not. Sometimes, too, patients have multiple lesions and you have to be sure to find them all with the probe.” Not
for Screening Most cancers reported in the Radiology study and in Neoplasis Press (September/October 2003) were early-stage and small—approximately 1 centimeter in diameter. Only one lesion measured 2.2 centimeters in diameter. The study the researchers reported in Neoplasia Press (March) involved six large breast carcinomas found among patients at the University of Connecticut Health Center (UCHC). Six patients with tumors ranging from 2.5 to 4 centimeters were studied. Again, using a handheld hybrid probe consisting of an ultrasound transducer and an NIR source detector, researchers were able to quantify the total hemoglobin distributions of their tumors and correlate the hemoglobin distributions with the microvessel density counts obtained from histology. Researchers were also able to quantify hypoxia, which is related to the growth rate and chemotherapeutic responsiveness of tumors. Future
Possibilities A major advantage of optical tomography over other techniques used to determine whether a suspicious area is malignant is “that near-infrared systems are cost effective, portable, and easily coupled to clinical ultrasound systems for repeated imaging,” Zhu says. Several other techniques, including computed x-ray tomography, PET, and MRI can be used to measure response to therapy, but they are more expensive to use for repeated scanning. NIR optical tomography may be the ideal noninvasive diagnostic and treatment monitoring technique because it is low cost and has no side effects, Zhu says. She also notes that more research is required. “We’re looking to do a study where we image about 600 to 1,000 patients at multiple hospital sites,” Zhu says. Significant contributors to the series of studies include Scott H. Kurtzman, MD; Susan Tannenbaum, MD; Mark Kane, MD; Poornima Hegde, MD; Bipin Jagjivan, MD; and Kristen Zarfos, MD, from the University of Connecticut Health Center; Edward B. Cronin, MD; Allen A. Currier, MD; and Hugh S. Vine, MD, from Hartford Hospital; and Minming Huang, PhD; NanGuang Chen, PhD; and Chen Xu, MS, from the Optical and Ultrasound Imaging Lab of the University of Connecticut. —
Beth W. Orenstein is a freelance medical writer who lives in Northampton,
Pa., and a frequent contributor to Radiology Today.
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