Breast MRI: What It Takes

Despite its success in discovering early-stage breast cancer, mammography is not perfect. For example, it fails to reveal the full extent of many cancers, and it overlooks others entirely. So considerable effort has been expended on trials of other imaging modalities; one that has been particularly successful is dynamic magnetic resonance imaging (MRI), which has shown almost 100% sensitivity in several studies.¹ In fact, MRI is capable of detecting cancers invisible to physical examination, mammography, and ultrasonography,² and its 3D capabilities improve the accuracy of lesion measurements. As more centers have begun using the technology, the American College of Radiology (Reston, Va) has issued a BI-RADS primer, which should reduce the past confusion caused by the lack of standardization in interpretation.³ Although its cost and inability to depict microcalcifications are among the drawbacks militating against the use of MRI in routine breast-cancer screening, the modality has found a secure place in breast imaging, and the indications are expanding all the time.

Equipment Needs

Vacuum-assisted needle biopsy system is an optional component of the dedicated breast 1.5T MRI.

Breast MRI is demanding. Although one large trial was carried out at 1.0T,⁴ and 0.6T scanners may be suitable for some applications,⁵ the general view is that a 1.5T scanner is required. (The Aurora scanner, the only machine designed specifically for breast imaging, is a 1.5T system.) Exploratory work is being conducted with 3.0T machines,⁶ but it is not yet clear what place these high-field machines will have in routine clinical practice. Breast MRI requires high temporal and spatial resolution with a large field of view. The scanner must be capable of repetitions within less than 2 minutes to capture the inflow and outflow of contrast medium,⁷ and submillimeter voxel sizes (such as spatial resolution of 1.2 mm² to 1.4 mm² in plane and 1.5 mm through-plane¹) and slice thicknesses of 3 mm or less are required. The scan also requires reliable fat-suppression and postcontrast-subtraction capabilities.

Dedicated Breast 1.5T MRI from Aurora Imaging Technology (North Andover, Mass).

“There still are sites that do one breast at a time: one breast one day, then having the woman return another day to evaluate the other breast,” according to Edward Hendrick, PhD, research professor and director, Breast Imaging Research, at Lynn Sage Comprehensive Cancer Center in Chicago and a member of the American Cancer Society Guidelines Committee for Breast Cancer Screening. “That means another injection of gadolinium, which is inappropriate and should not be necessary.” Indeed, it often is argued that bilateral examinations are mandatory. Single-breast studies take longer and are more costly because of the need for a second gadolinium injection and more nursing care. There also is a greater risk of adverse reactions. Bilateral studies are easier to perform and interpret, and they increase patient satisfaction. In premenopausal women, they also ensure that any changes in the breasts caused by the menstrual cycle will be identical in both images.¹ Even if a breast is being examined for a known cancer, bilateral studies are advantageous, both to facilitate interpretation and because a cancer may be present in the contralateral breast that will be missed if only the index lesion is examined.

“Any site wishing to do breast MR either needs to be able to do MR-guided biopsies or have a convenient referral site that can,” Hendrick stressed. “Some radiologists are good at finding MR-visible lesions with ultrasonography once they know where to look, but eventually—especially if you screen high-risk patients—you will need to sample something that is not visible on ultrasound or mammography.” Vacuum-assisted biopsy tools are preferred by many radiologists.

Current Indications for Breast MRI

So where does MRI fit into breast imaging today? The most common indications are problem solving after mammography, assessing the extent of a known primary tumor (including examination of the contralateral breast and lymph nodes for cancer), determining the response to neoadjuvant chemotherapy, and detecting occult primary tumors.

Problem-solving trials have looked intensively at the rate, extent, and pattern of lesion enhancement after gadolinium injection. An abnormality is described according to its nature (focus, mass, nonmass).³ Masses, in turn, are described according to their shape, type of margin, and enhancement characteristics, which are classified into six types, such as rim or central. Rules also have been formulated for describing the kinetics of contrast enhancement.³ In a multicenter trial examining 995 suspect lesions in 854 patients, absence of enhancement in response to gadolinium contrast had an 88% negative predictive value for cancer; that is, no enhancement generally means a mass is benign.⁸ On the other hand, a focal margin and increased signal intensity after contrast injection was highly predictive of malignancy. In another series,⁷ signal-intensity increases of more than 100% were seen in about three fourths of ductal carcinomas in situ and nearly all invasive carcinomas. An ex vivo study indicated that enhancement patterns often can distinguish among various histologic types of cancer.⁹

Some reports have suggested that the MRI can reveal histologic features with prognostic significance. Andrea Teifke, MD, and her colleagues at Johannes Gutenberg University of Mainz studied rim enhancement and microvessel density, measured using Adobe Photoshop, in 86 malignant and 32 benign lesions and found that such enhancement reflected a higher microvessel density at the periphery than in the center of cancers.⁴ Tumors with strong rim enhancement were likely to be estrogen-receptor negative. There was some indication that earlier rim enhancement and faster washout of contrast was evidence of histologic features of poor prognosis. Those investigators cautioned, however, that some benign lesions, particularly hyperplastic and inflammatory ones, also enhance. M. Jinguji and colleagues of the Department of Radiology at Kagoshima University in Japan¹⁰ examined the pattern of rim enhancement in relation to the histopathologic features of known cancers and found rim enhancement to be more common in larger invasive carcinomas of higher grade. When enhancement progressed centripetally, there was a higher risk of lymph-node metastases and a lower likelihood of estrogen-receptor positivity. Persistent rim enhancement forecast a finding of receptor-negative tumor.

Maximum intensity projection of a lateral breast MR image (left) provides 3D viewing capability to help localize tissue and its relationship to other anatomy and angiogenesis map (right) produced by the CADstream CAD program from Confirma (Kirkland, Wash) was developed in accordance with the BI-RADS to promote standardization.

There is growing evidence of the value of computer-aided diagnosis. At the 2005 Radiological Society of North America (RSNA of Oak Brook, Ill) Scientific Session, Joan C. Vilanova, MD, and his colleagues at the Clinica Girona in Girona, Spain, reported a comparison of a computer-aided detection system and the onboard breast-imaging analysis software from an MRI scanner.¹¹ Use of the CAD software increased the sensitivity to known tumors from 89% to 95% with no loss of specificity (66% for both modalities). Moreover, the tumor measurements obtained by CAD were more accurate than those of the standard software, as judged by the pathologist’s measurements, and the time required by the radiologist to assess the tumor declined from 17 minutes to 5 minutes with CAD.

Another team reported on CADstream, a program from Confirma Inc of Kirkland, Wash.¹² CADstream produces overlays of different colors to mark the speed of contrast inflow and washout on the basis of defined thresholds (such as 50%, 80%, or 100% change). At the RSNA Annual Meeting, Wendy B. DeMartini, MD, from the University of Washington and the Seattle Cancer Care Alliance discussed the results in 154 lesions detectable only by MRI. Use of the analytical software reduced false-positive interpretations by as much as 50%. (An extended version of this report has since been published.²) In the opinion of this team, CAD software may reduce the number of biopsies that yield only benign tissue with no reduction in the accuracy of cancer detection, greatly improving the utility of MRI in problem solving.²

A promising approach to clarifying the precise nature of a lesion is MR spectroscopy. In a trial at Memorial Sloan-Kettering Cancer Center in New York, 57 lesions with a median size of 2.3 cm in 56 patients were examined by proton spectroscopy with analysis of choline.¹³ All cancers had a choline peak. The method thus proved to have a sensitivity to cancer of 100%. The specificity was 88%, with only three of the 26 known benign lesions having choline peaks. The investigators noted that use of the technique would have increased the positive predictive value of biopsy from 35% to 82% and that if only lesions with a choline peak had been subjected to biopsy, 23 of the 40 benign lesions would not have been biopsied, and no cancers would have been missed.

The growing demand for breast-conserving treatment has created pressure for preoperative definition of the extent of a cancer, which often is not shown by mammography. A North American?European study sought to detect tumors more than 2 cm distant from the first confirmed cancer.¹⁴ MRI detected significantly more such lesions than did mammography, and the investigators concluded that MR probably should precede any breast-conserving operation. MR also has proved helpful after lumpectomy with positive margins at differentiating residual tumor from scar.

The drive to conserve breast tissue also has led to the practice of neoadjuvant chemotherapy, in which an attempt is made to shrink a locally advanced tumor before surgery. However, this protocol can delay necessary surgery or changes in chemotherapy by 6 months or more if the initial drug regimen proves inactive against the patient’s disease. Investigators in the United Kingdom and Japan have tested various MRI techniques for utility in early definition of nonresponsiveness. In a study at the University of Hull, quantitative MR and proton MR spectroscopy were tested. Changes (or lack thereof) in the tissue water—fat peak area and the water T2 after the second chemotherapy cycle—were predictive of the final tumor response in 70% of the women.¹⁵ At the Royal Marsden Hospital, dynamic MRI with measurement of size and the transfer constant after the second chemotherapy cycle were accurate predictors of the eventual response, with 100% sensitivity and specificity of 90% for size and 75% for the transfer constant.¹⁶ In a study at Osaka University, MRI with 3D maximum-intensity projection reconstruction proved more accurate in determining lesion size than mammography with caliper measurements and ultrasonography, both of which tended to overestimate the true tumor response, as judged by physical measurements of the resected tumor.¹⁷ The American College of Radiology Imaging Network (ACRIN of Philadelphia) has a clinical trial in progress of dynamic MRI as an intermediate measure of treatment impact with a focus on new drug regimens and locally advanced cancers (ACRIN 6657).

T. Kazama and colleagues at Chiba University Hospital in Japan sought to learn whether MRI could detect invasion of the pectoralis muscle.¹⁸ They performed contrast-enhanced examinations with 3D gradient-echo sequences and slice thicknesses of 1.5 or 2 mm in 306 women and found disruption of the fat plane between the tumor and the muscle in 33 instances. In seven cases, enhancement of the muscle adjoining the disruption was noted, and in six of these patients, the tumor was found at surgery to have invaded the muscle. The sole false-positive case was the result of a previous biopsy. Disruption of the fat plane, by itself, is not indicative of tumor, the investigators concluded, whereas disruption with enhancement of the adjoining muscle usually indicates invasion by the tumor.

Screening of high-risk women and women with dense breasts is one of the most popular uses of breast MRI, although available evidence is not sufficient to earn a recommendation of the practice from the American Cancer Society.¹⁹ Several clinical trials of MRI as an adjunct to mammography are in progress in this indication. Two recent publications suggest the potential. The Breast Imaging Section at Memorial Sloan-Kettering Cancer Center used MRI in 367 high-risk women with normal mammograms.²⁰ Among the 59 patients undergoing biopsy for suspect MR findings, 14 cancers were discovered; and overall, 4% of the women were found to have breast cancer. More than half of the cancers were ductal carcinoma in situ, an unexpected finding in this population. The MR examination seemed particularly useful in women with a family history of breast cancer and those who had undergone breast-conserving surgery for an earlier cancer. An extensive analysis with a computer model at Stanford University (Stanford, Calif) suggested that dynamic MRI is cost-efficient as an addition to mammography in women with a BRCA1 or BRCA2 mutation, with a cost per quality-adjusted life-year of $55,420 in the former group and $130,695 in the latter.²¹

MRI has proved valuable for locating clinically and mammographically occult primary lesions, as shown by two studies at Memorial Sloan-Kettering Cancer Center in New York. In a series of 69 women with axillary adenopathy or metastases, MRI identified 42 lesions, 62% of which proved to be the occult cancer.²² Slightly more than half of these women turned out to be candidates for breast-conserving surgery. The MR study also found the primary lesion in half of the women with distant disease. In another 57 women with what proved to be 68 cancers, dynamic MRI revealed the mammographically occult, nonpalpable tumors, many of which appeared as enhancing diffuse areas rather than masses.²³

The Future

The possible future place of breast MR is demonstrated by a review of 82 women at Hadassah Medical Center in Israel. In this series, MRI scans had an impact on the clinical course of 62 patients, stimulating performance of other studies in 15 women and causing a change in the treatment plan in nine.²⁴ The ability of MR to measure tissue temperature may find it a role in localized thermoablation with high-intensity focused ultrasound.²⁵ Clearly, MRI is now a well-established modality for examination of the breast.

Judith Gunn Bronson, MS, is a contributing writer for Medical Imaging.

References

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