Breast Cancer

Invasive breast tumors are characterized by an ingrowth of neovascularity at their periphery. Tumor angiogenesis is associated with increased perfusion and abnormal leaky endothelium, leading to preferential enhancement of tumors versus normal breast tissue (Box 7-1). With bolus administration of an intravenous (IV) contrast agent, increased vascular flow and the rapid exchange rate of contrast between blood and the extracellular compartment cause invasive breast tumors to enhance more rapidly and more avidly than normal fibroglandular tissue, even in patients with dense breasts. Thus, invasive breast cancers have high signal intensity and are brighter than the surrounding normal tissue on the first postcontrast scan, which ideally should be obtained about 90 seconds after injection. As a result, MRI exquisitely reveals invasive tumors that are occult on mammography (Fig. 7-1). The sensitivity of MRI for invasive breast cancer is extremely high—over 90%. However, as discussed in detail in this chapter, contrast enhancement on MRI is seen in many benign conditions as well; the specificity of MRI varies between 39% and 95%. As detailed in this chapter, morphology, T1 and T2 characteristics, and the time course of contrast enhancement help differentiate benign from malignant lesions (Table 7-1).

Figure 7-1 Mammographically occult breast cancer. A, Mediolateral oblique mammogram in a woman with a palpable mass in the upper portion of the breast indicated by a metallic skin marker (arrow) revealed only dense tissue. B, Contrast-enhanced water-specific 3-D magnetic resonance image demonstrated a 1-cm rim-enhancing lesion (arrow). Lumpectomy revealed a 1-cm invasive ductal carcinoma.

Patient Preparation

Benign hormone-related enhancement of normal breast tissue, called background enhancement, occurs before the onset of menses and can lead to false-positive studies. When possible, patients should be imaged 7 to 10 days after the onset of their menstrual cycle, when spurious contrast enhancement of normal breast tissue is at its nadir (Box 7-2).

Before MRI scanning, the patient fills out an MRI safety form to exclude contraindications of entering the strong magnetic field, such as ferromagnetic vascular clips, metallic ocular fragments, pacemakers, and implanted electromechanical devices. A qualified person reviews the standardized MRI safety form before scanning (Fig. 7-2).

Figure 7-2 A and B, Magnetic resonance imaging (MRI) safety form. As part of routine safety interview procedures before MRI, patients fill out a history form to screen for implanted devices or other conditions that might affect the safety of MRI.

(Courtesy of Dr. Frank Shellock, MRI-Safety.com. Reprinted by permission.)

As with mammography, an MRI-specific breast history form is helpful to detail patient breast risk factors, family history, breast lumps, scars, or other areas of complaint. The technologist places MRI-compatible markers on the patient’s breast to indicate lumps or areas of concern and annotates them on the history form. The patient details the location, date, and results of previous breast biopsies because recent healing breast biopsies may normally show enhancement and are a cause of false-positive results. The patient also documents any use of exogenous hormone therapy and the phase of the menstrual cycle or menopause, because those factors may cause spurious background enhancement of normal tissue, which can produce false-positive results.

Equipment

An IV catheter is placed before scanning and is continuously flushed by using the keep vein open (KVO) setting of an MRI-compatible remote power injector. Placement of the catheter in the antecubital fossa contralateral to any known, previous, or suspected malignancy is preferred. The patient is placed prone on a dedicated breast coil (Fig. 7-3A). Prone positioning minimizes respiratory motion in the breast. Phased-array breast coils maximize the signal-to-noise ratio of the image. Patient discomfort is the primary cause of motion; the majority of patients remain most comfortable for the duration of the entire scan with both arms at their sides and wearing hearing protection (see Fig. 7-3B). The technologist spends considerable time discussing the importance of “holding still” with the patient to obtain the best scan. The patient then works with the technologist to obtain a comfortable position within the breast coil. Optional mild breast stabilization, or “compression,” may be used to reduce breast motion and decrease the volume of tissue to be scanned so that the whole breast is included. However, firm compression (as used routinely for mammography) should be avoided because it may negatively affect contrast enhancement. Scanners with a magnetic field strength of 1.5 Tesla (T) or 3.0 T provide the best signal-to-noise ratio. Magnets with high-performance gradients enable the fastest, highest-resolution scans (Box 7-3).

Figure 7-3 Dedicated breast coil and 1.5-Tesla (T) scanner. Prone positioning with the breasts in the apertures of a dedicated, phased-array breast coil (A) improves image quality by maximizing the signal-to-noise ratio of the image and minimizing respiratory motion. Imaging at 1.5 T enables more robust fat suppression and produces a higher signal-to-noise ratio than imaging at lower field strengths does. B, Conventional closed-bore scanners have stronger, faster gradient systems than open magnetic resonance imaging systems do; these systems enable faster scans with more slices and higher spatial resolution. Use of a remote power injector (arrow) enables administration of contrast during the dynamic scan protocol while the patient is within the magnet.

(A, Courtesy of Tom Tynes, MRI-Devices Inc, Waukesha, WI. Used by permission.)

MRI Protocols

Conventional breast MRI begins with T1-weighted images to define the position and anatomy of the breast. T1-weighted images using the signal from the “body coil” rather than the breast coil enable basic evaluation of the axillae, anterior mediastinum, chest wall, and supraclavicular fossa for enlarged regional lymph nodes. Thereafter, a dedicated breast coil signal should be used to perform all subsequent sequences. T2-weighted fast spin-echo (FSE) images are then obtained to characterize the breast and any lesions. T2-weighted scans using an FSE, turbo spin-echo (TSE), or rapid acquisition with relaxation inhibition (RARE) technique, produce high-quality images within reasonable scan times of 5 to 6 minutes. High fat signal on T2-weighted FSE images can be prevented with fat suppression and is most successful if unilateral scanning is performed (Table 7-2).

Table 7-2 Basic Bilateral Protocol for Breast Cancer MRI

Sagittal imaging for all scans except series 1 allows smallest field of view (∼20 cm for most patients) and thus highest resolution.

Frequency encoding in the anteroposterior direction minimizes artifacts from cardiac and respiratory motion in the breast.

Series in brackets are optional, and not yet standard of care.

1H, proton (hydrogen nucleus); ADC, apparent diffusion coefficient; EPI, echo-planar imaging; FOV, field of view; FSE, fast spin echo; Gd-DTPA, gadolinium diethylenetriamine pentaacetic acid; IPAT, integrated parallel acquisition techniques; NEX, number of excitations or signal averages; RARE, rapid acquisition with refocused echoes; SENSE, sensitivity encoding; STIR, short tau inversion recovery; TE, echo time; TR, repetition time; TSE, turbo spin echo.

* T2: Fast spin-echo (FSE, RARE, TSE, etc.) with effective TE 80–100 ms and TR at least 3000 ms provides good T2 weighting. Use 3- to 4-mm-thick slices and 256×192 matrix or higher for small FOV sagittal images. Fat saturation improves conspicuity of bright lesions on T2, although nonfat-suppressed T2 imaging allows fat signal intensity to be used as a reference signal intensity. Volume shimming improves fat suppression.

^† B-values have not been standardized yet, but most investigators use 500–1000 with good results. Parallel imaging may reduce distortions in echo planar imaging.

^‡ Both fat suppression and high spatial resolution (<2 mm in all directions) are essential to assess lesion morphology. Rapid imaging (60–90 sec per scan or less) is necessary to assess contrast uptake kinetics. Use “fast” spoiled 3-D gradient echo (TR ≤ 6 ms; FA ∼ 15° for T1 weighting). Intermittent “special” fat saturation pulses speed imaging substantially over conventional fat saturation. Fractional k-space (“1/2 NEX,” etc.), and parallel imaging (SENSE/IPAT, etc.) maximize resolution obtained during the limited scan time.

^§ Repeat rapidly for dynamic scans totaling approximately 7 minutes or more. Inject 0.1 mmol/kg standard low molecular weight gadolinium contrast agent (e.g., Gd-DTPA, gadoteridol, etc.) at 2 mL/sec followed by 20 mL flush (normal saline) at the start of the acquisition. Avoid negatively charged gadolinium agents if protocol includes spectroscopy, because they may reduce choline signal. (Lenkinski B, Wang X, Elian M, Goldberg SN: Interaction of gadolinium-based MR contrast agents with choline: implications for MR spectroscopy (MRS) of the breast, Magn Reson Med 61(6):1286–1292, 2009.

^¶ Single-voxel choline spectroscopy. A minimum voxel size of 1 cm × 1 cm × 1 cm is recommended for adequate signal-to-noise. Localized shimming and high-quality spatial saturation pulses, fat suppression, and partial water suppression improve quality of spectra.

Considerable variation exists worldwide in methods used for the contrast-enhanced portion of the examination. Most investigators agree that both the time course of enhancement provided by dynamic scanning and the morphology of lesions revealed by high-spatial resolution scanning provide distinct and useful information about the risk of malignancy in enhancing lesions. However, commercially available MRI pulse sequences necessitate a compromise between the dynamic and high-spatial resolution approaches. Currently, most scans are done with repeated T1-weighted, fat-saturated, 3-D spoiled gradient-echo (SPGR) scans. Slice thickness and resolution are selected to give maximum resolution and bilateral whole-breast coverage within a 60- to 90-second scan duration. Parallel imaging and intermittent/partial fat saturation substantially speed up imaging, allowing much higher resolution within the same scan time.

Volumetric T1-weighted 3-D SPGR imaging is repeated as rapidly as possible before, during, and for approximately 5 to 7 minutes after administration of a rapid IV bolus of 0.1 mmol/kg gadolinium contrast agent. Most investigators use axial or coronal images with a rectangular field of view to maximize efficiency. Images may be processed by subtracting the precontrast baseline images from subsequent dynamic images to reveal areas of enhancement. Region-of-interest analysis is used to assess the time course of contrast enhancement. Subtraction processing suppresses signal from bright fat because adipose tissue does not enhance significantly. Spatial resolution is limited by the need for rapid scan times and the large field of view required for bilateral scanning.

Proper shimming of the magnet and choice of center frequency are essential to ensure adequate fat suppression. Bilateral high-spatial resolution imaging is now possible on most scanners because of the development of hardware and software required for bilateral shimming and because coverage is possible with reasonable scan times.

In bilateral combined dynamic and high-spatial resolution imaging, sophisticated protocols and scanning techniques capture both rapid dynamic and high-spatial resolution images of both breasts during and after IV contrast injection. Approaches include time-resolved imaging of contrast kinetics (TRICKS) and interleaved protocols, in which dynamic scanning is interrupted for high-spatial resolution imaging. These protocols provide very high-quality images but they require rapid switching between different pulse sequences.

The American College of Radiology (ACR) now has guidelines for the performance of breast MRI and in 2010 launched a breast MRI accreditation program. The ACR MRI program recommends that facilities be able to obtain bilateral studies and be able to perform MRI-guided biopsies.

Normal Breast MRI Findings

Typical images from a normal patient who underwent both bilateral dynamic and high-spatial resolution imaging are provided in Figure 7-4. On T1-weighted noncontrast-enhanced images, aqueous tissues (including skin, fibroglandular tissue, muscle, and lymph nodes) have moderately low signal intensity when compared with the higher signal intensity of fat, which has a short T1 relaxation time. In the absence of previous surgery or pathology, a layer of subcutaneous and retromammary fat completely surrounds the mammary gland tissue except where it enters the nipple–areola complex. The mammary gland itself is composed of a mix of low-signal fibroglandular tissue and high-signal fat lobules. The mix and distribution of fat and fibroglandular tissue vary greatly between patients—from dense, uniformly glandular tissue with almost no visible fat, to heterogeneous, to predominantly fatty tissue separated by thin strands or septa of fibroglandular tissue. In the ACR Breast Imaging Reporting and Data System (BI-RADS®) MRI lexicon the amount of dense glandular tissue by volume is described in the same terms as used in the mammography lexicon. These include almost all fat (0% to 25% dense), scattered fibroglandular tissue (25% to 50% dense), heterogeneously dense (50% to 75% dense), or dense (>75% dense) (Box 7-4 and Fig. 7-5).

Figure 7-4 Normal breast magnetic resonance imaging (MRI). A, Axial T1-weighted spin-echo images reveal high-signal fat within the breast and axilla. Soft tissues, including skin, fibroglandular tissue, lymph nodes, and muscles, are dark. B, Sagittal, fat-saturated, T2-weighted fast spin-echo images reveal dark signal within fat and moderately low signal within the pectoralis muscle. Glandular tissue has mixed T2-weighted signal intensity. C, Precontrast water-specific 3-D spectral-spatial excitation magnetization transfer (3DSSMT) reveals dark fat and moderately low fibroglandular and muscle tissue signal. D, High-spatial resolution 3DSSMT after the intravenous administration of a 0.1-mmol/kg bolus of contrast reveals enhancing peripheral vessels (arrows) and mild nipple enhancement. E, Rapid dynamic 3-D spiral imaging reveals mild (<50%) gradual enhancement in the nipple and fibroglandular tissue and mild (<50%) rapid enhancement in the pectoralis muscle (F). Subtraction processing of early postcontrast multiplanar two-dimensional spoiled gradient echo images (G) minus precontrast baseline images (H) reveals diffuse low-level fibroglandular and muscle enhancement.

Figure 7-5 Examples of normal breast magnetic resonance imaging (MRI) density by volume on noncontrast sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) scans. A, Fatty sagittal postcontrast MRI shows mostly fatty tissue (0% to 25% density). B, Scattered fibroglandular tissue (25% to 50%). C, Heterogeneously dense breast tissue (50% to 75%). D, Dense glandular tissue (>75%).

T2-weighted noncontrast-enhanced images reveal heterogeneous fibroglandular tissue that is usually higher in signal intensity than adjacent muscle but still not as bright as the small subcutaneous blood vessels commonly seen at the periphery of the breast or as pure fluid (i.e., cysts, ducts).

After contrast injection, normal glandular tissue enhances to variable degrees. Normal fibroglandular breast tissue enhancement is called background enhancement in the BI-RADS® lexicon. An understanding of normal background enhancement is important because normal background enhancement can obscure cancers and make the MRI harder to read. Background enhancement describes slowly enhancing breast tissue within the breast. Specifically, normal fibroglandular tissue enhances with nonmasslike patterns, including stippled enhancement (tiny <5 mm foci of enhancement separated by normal tissue); scattered, regional, or multiple regions; or diffused stippled enhancement throughout both breasts. The areas of enhancement are usually separated by nonenhancing normal breast tissue between the normal background enhancing foci. In the BI-RADS® lexicon, the amount of background enhancement is described as a percentage of enhancing breast tissue with respect to the volume of the entire breast. Background enhancement is categorized in quartiles. The descriptors include none (0%), minimal (1% to 25%), mild (25% to 50%), moderate (50% to 75%), and marked (>75%) (Box 7-5 and Fig. 7-6).

Figure 7-6 Background enhancement on contrast-enhanced breast magnetic resonance imaging (MRI). A, No abnormal background enhancement. Contrast-enhanced breast MRI shows that the scant glandular tissue does not enhance. There is enhancement of an axillary lymph node. B, Minimal enhancement. Scattered fibroglandular tissue with minimal background enhancement. C, Mild enhancement. Scattered fibroglandular breast tissue with mild background enhancement. D, Heterogeneously dense tissue with moderate background enhancement. E, Marked enhancement. Dense glandular tissue with marked background enhancement.

The amount of background enhancement depends on the patient’s hormonal status, stage of the menstrual cycle, and whether the patient is premenopausal or postmenopausal. For example, in premenopausal women, normal breast tissue enhances the most right before the onset of menses. The normal breast tissue enhances the least 7 to 10 days after the onset of menses. Postmenopausal women on exogenous hormone therapy may enhance greatly. However, the amount of background enhancement depends not only on how much the tissue enhances, but also on the actual volume of dense breast tissue present. For example, a woman with extremely dense breast tissue, in which most of the breast is composed of fibroglandular tissue, may enhance from 0% to 100%. This woman might have minimal to marked background enhancement, because more than 75% of her breast is capable of enhancing. However, if the breast has only scattered fibroglandular tissue (25% to 50% dense), the greatest amount of background enhancement possible is mild background enhancement, or 25% to 50% enhancement, because only 25% to 50% of the breast is dense enough to enhance within and the remaining 50% is fat. Of note, cancers can occur in both dense and fatty parts of any breast.

Reporting normal background enhancement gives a clinician and other radiologists an idea of how likely it would be for the normal enhancing structures to hide a breast cancer and how confident the radiologist is in detecting breast cancer on the MRI.

After contrast injection, peripheral small subcutaneous vessels, the nipple, and adjacent retroareolar tissue enhances to variable degrees. The normal nipple enhances along its edge in a thin line; the rest of the nipple is dark, with an occasional dot of enhancement centrally within the nipple itself. The areolar complex is dark on the normal MRI. The normal skin is 2 to 3 mm in thickness and enhances slightly.

The rate and degree to which findings enhance gives a clue to whether the finding is normal or malignant. Dynamic imaging shows that fibroglandular tissue enhances mildly and slowly. Nipple enhancement curves are more avid, but still gradual. Muscle enhances rapidly at first, but never enhances very avidly. Subtraction imaging of a normal breast should show mild glandular and muscle enhancement. Usually cancer is much brighter than the background enhancement and will look much brighter on the first postcontrast scan compared to normal tissue. Normal breast tissue kinetic curves show a slow initial rise and a late persistent plateau. This normal slow initial and late persistent curve helps to distinguish normal breast tissue from cancers. Cancers will usually enhance rapidly initially, with a washout or a plateau of signal intensity in the delayed phase.

Common Breast MRI Artifacts

Ghosting from cardiac or respiratory motion occurs in the phase-encoding direction (Table 7-3). It can be prevented from obscuring breast tissue by careful selection of phase- and frequency-encoding directions. Poor fat suppression is usually due to poor shimming or incorrect choice of the excitation center frequency, especially in patients with silicone implants (Fig. 7-7) or non–MRI-compatible objects, such as BB markers, magnetic tissue expanders, scar markers, and metal infusion ports, in or near the breast. Patient motion may cause blurring of the image, so it is especially important that the patient hold still and breathe quietly during scanning. On subtraction imaging, patient motion causes alternating bright and dark bands at fat–glandular tissue interfaces (see Fig. 7-7).

Table 7-3 Common Artifacts

Figure 7-7 Common imaging artifacts. A, Inconsistent fat suppression on water-selective images is due to poor shimming or incorrect selection of the center frequency (arrow), or both. B, Repeat shimming and tuning improve fat suppression. C, Poor fat suppression on subtraction images is due to patient motion, causing misregistration artifacts at fat–skin or fat–glandular interfaces (arrows).

Poor breast tissue enhancement may be due to failed contrast injection, which can be confirmed by abnormal dynamic enhancement curves from the heart. The heart usually shows normal rapid, avid initial enhancement and rapid washout. In fact, one of the most common errors in contrast-enhanced breast MRI is the result of a poor bolus of IV contrast. Sometimes, the IV line is injected slowly or may even become detached from the vein; as a result, the contrast never enters the patient. To ensure rapid uptake of contrast and washout of signal intensity within the heart, one checks a region of interest over the heart or a large artery for a rapid intake bolus and late washout on the kinetic curve. This is important because only a good bolus of contrast will translate into breast cancer enhancing rapidly on the MRI scans. An abnormal or poor cardiac kinetic curve tells the radiologist that something is wrong with the contrast injection; further investigation is needed to determine why contrast in the heart did not rise in signal intensity rapidly and washout as expected. Scans that show poor contrast enhancement in the heart indicate a problem with the contrast injection and cannot be trusted to show cancer in the breast (Fig. 7-8).

Figure 7-8 Invasive ductal cancer (IDC) on ultrasound and signal void on postcontrast sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) magnetic resonance imaging (MRI) scans, missed because of late imaging. A, In the outer left breast, a focal asymmetry with possible spiculations (arrow) within dense fibroglandular tissue is seen only on the craniocaudal view. B, Left breast ultrasound shows a very hypoechoic irregular suspicious breast mass corresponding to the density seen in part A. C, Postcontrast sagittal 3DSSMT shows heterogeneously dense breast tissue and marked background enhancement in the left breast. There is signal void from the marker placed in the IDC in the upper breast, but the cancer itself is not seen, possibly obscured by the marker or the surrounding background enhancement. However, it was noted that the scan was delayed and the imaging was done in a later phase approximately 10 minutes after injection. A repeat MRI was done. D, Postcontrast sagittal repeat 3DSSMT shows marked background enhancement in the left breast, but because this scan was done at minutes, it shows an enhancing tumor at the signal void (arrow). E, In addition, a 6-mm mass is noted inferior to the main cancer; this was not seen previously and was undetectable in the background enhancement (arrow).

Breast Lesions: Approach and Lexicon

Initial studies of contrast-enhanced MRI reported a sensitivity of more than 90% for invasive breast cancer. The sensitivity of contrast enhancement has remained high for invasive breast cancer. However, achieving high specificity remains difficult because some benign breast conditions enhance more avidly than normal breast tissue and may resemble breast cancer. Specifically, benign fibroadenoma, papilloma, and proliferative fibrocystic change also enhance to a greater degree than normal surrounding breast tissue.

To interpret studies of lesions on MRI, radiologists use a combination of high-spatial resolution scanning (which produces sharp images for analysis of abnormally enhancing findings or produces analysis by lesion morphology) and dynamic imaging (which produces the kinetic curves of an abnormally enhancing finding). In addition, T2-weighted imaging plays a secondary role in distinguishing some benign and malignant lesions (Table 7-4).

Table 7-4 T2-Weighted Imaging of Breast Lesions

* The exceptions are rare mucinous carcinomas and some invasive ductal cancers, which may enhance and have high T2 signal; irregular, rim-enhancing morphology and dynamic enhancement curves may help with diagnosis.

Morphology

In the high-spatial resolution approach, lesion morphology is evaluated on fat-nulled, 3-D images to look for characteristic shapes, borders, or internal enhancement patterns characteristic of cancer. With this approach, Nunes and colleagues reported a sensitivity of 96% and a specificity of 80% for cancer. Leong and colleagues reported similar results. The morphologic characteristics of benign and malignant lesions are summarized in Table 7-1 and Box 7-6, and are shown in Figure 7-9. As discussed elsewhere in this chapter, the radiologist first decides if the finding is a mass or a nonmasslike enhancement. Consistent with mammography, masses with spiculated or very irregular borders are suspicious. Bright enhancement, particularly rim enhancement and enhancing septations, is usually suspicious for tumor angiogenesis. A ductal, linear, or segmental pattern of clumped enhancement is suspicious for ductal carcinoma in situ (DCIS), but it can also be seen in benign duct ectasia or fibrocystic change. As with mammography, entirely smooth, oval, or lobulated masses oriented parallel to Cooper ligaments suggest benign lesions, whereas lesions traversing Cooper ligaments are abnormal and suggest invasive ductal cancer. Nonenhancing internal septations in smooth, oval, or lobulated masses are highly specific for a benign fibroadenoma. Nonenhancing lesions are also benign. However, it is important to evaluate the dynamic curves of benign-appearing enhancing masses because round or oval homogeneous cancers mimic benign fibroadenomas. Sometimes the suspicious kinetic curves may be the only clue that the morphologically benign mass is a cancer.

Figure 7-9 Morphologic features suggesting malignancy include spiculation (A), rim enhancement (B, detail from Fig. 7-1B), and enhancing internal septations (C, arrow). Morphologic features suggesting benignancy include smooth borders (D) and nonenhancing internal septations (E, arrow).

Dynamic Contrast Enhancement

In the dynamic MRI approach, one evaluates a lesion’s signal intensity as a function of time during the bolus IV administration of contrast material (Box 7-7). The dynamic curves are evaluated according to initial and late enhancement. Initial enhancement describes the curve in the first 2 minutes during the bolus or when the curve begins to change. The late phase of enhancement occurs after the first 2 minutes or after the curve starts to change. The late-phase curve is described as persistent, plateau, or washout, in keeping with the ACR BI-RADS® MRI lexicon. The entire spectrum of the time course of enhancement may be categorized from most benign to most suspicious, according to the following scheme of Daniel and colleagues (Fig. 7-10): nonenhancing (type I), gradually enhancing (type II), or rapidly enhancing with a sustained gradual enhancement, plateau, or early washout (types III, IV, and V, respectively). In reference to the curve shapes depicted in Figure 7-7, types I and II typically indicate benignancy and types IV and V indicate a high likelihood of malignancy. Type III curves are indeterminate. Using a similar approach, Kuhl and colleagues reported a sensitivity of 91% and a specificity of 83%. Kuhl type I curves are gradually enhancing with a late persistent plateau. Kuhl type II curves are rapidly enhancing with a late plateau. Kuhl type III curves are rapidly enhancing with a late rapid washout. There are a few exceptions to these general principles. DCIS may exhibit any of the curve types, including nonenhancing or gradually enhancing curves, shown as types I and II in Figure 7-7. Benign papillomas may exhibit type I, II, III, or even type IV curves shown in Figure 7-7. The geographic distribution of dynamic enhancement also appears to be predictive, with tumors usually enhancing most rapidly at their periphery and benign lesions enhancing most rapidly at the center.

Figure 7-10 Classification of the time course of dynamic contrast enhancement from the most likely benign (type I) through the most likely malignant (type V). No enhancement (type I) or gradual enhancement (type II) suggests a benign lesion. Rapid initial enhancement followed by gradual late enhancement (type III) is indeterminate. Rapid initial enhancement followed by a plateau signal intensity (type IV) or early washout of signal intensity (type V) is suspicious for invasive malignancy.

(From Daniel BL, Yen YF, Glover GH, et al: Breast disease: dynamic spiral MR imaging, Radiology 209:499–509, 1998.)

A variety of image-processing techniques have been developed to automate analysis of dynamic images throughout the breast on a pixel-by-pixel basis, including the saturation model, the two-compartment pharmacokinetic model, the “three time point method,” and simpler enhancement ratios, wash-in slopes, and washout rates. Stand-alone workstations are available to perform these calculations and produce “functional images” that display abnormal areas of dynamic enhancement on corresponding anatomic images. Most current software determines whether to colorize a lesion based on whether it exceeds a percentage enhancement threshold at approximately 1 minute. The color of the lesion is set to reflect the late enhancement dynamics (i.e., persistent, plateau, and washout).

Not surprisingly, the highest sensitivity and specificity arise when both morphologic information and dynamic enhancement curves are taken into account, with a sensitivity of 95% and a specificity of 86% reported by Daniel and colleagues and a sensitivity of 91% and a specificity of 83% reported by Kinkel and colleagues. Pharmacokinetic scans or physiologic scans are scans that superimpose physiologic information, such as enhancement information, on morphologic images, thereby combining both types of information into one format. This type of scan usually shows the morphologic appearance of a lesion with the physiologic image superimposed in color.

T2-Weighted Imaging

T2-weighted imaging also plays an important role in discriminating which enhancing lesions are likely to be benign or malignant (Fig. 7-11; see also Tables 7-1 and 7-4). Lesions with very high signal, in which the lesion is much brighter than glandular tissue and even higher than fat on nonfat-suppressed T2-weighted FSE images, suggest benign lesions such as cysts, fluid-filled ducts, lymph nodes, or fibroadenomas. Invasive tumor, on the other hand, usually has a T2 signal similar to that of glandular tissue, that is, higher than muscle but not as high as fluid. Low-signal septations within very high-signal smooth oval or lobulated lesions on T2-weighted imaging also suggest benign fibroadenomas. Exceptions to this “rule” include mucinous cancer, which can be very bright on a T2-weighted image. Some invasive ductal cancers also may be bright on T2-weighted images. These T2-bright cancers may show irregular margins and inhomogeneity; however, it is important to check kinetic curves on all masses because occasionally cancer may be round or oval and have smooth borders.

Figure 7-11 T2-weighted imaging features of benign and malignant disease. Very high signal on T2-weighted fast spin-echo images that is brighter than fat (on nonfat-suppressed sequences) and substantially brighter than glandular tissue suggests a benign lesion such as a cyst (A, arrow), intramammary lymph node (B, arrows), or fibroadenoma (C). Low-signal septa are particularly specific for fibroadenoma (see Fig. 7-18A). D, Most malignancies, unless frankly necrotic, have a signal intensity that is similar to that of fibroglandular tissue (arrow).

Breast MRI Atlas

Table 7-6 shows a simplified guide to breast MRI interpretation.

Benign Breast Conditions

Fluid-filled cysts and milk ducts are normal and occur frequently (Fig. 7-14). Simple cysts are round or oval with sharp margins. Adjacent cysts may be separated by thin, low-signal septations. Simple cysts have very high T2 signal and display no internal enhancement with contrast, although a faint thin rim of gradual enhancement may be seen on high-resolution images. Occasionally, benign cysts may demonstrate high signal on unenhanced T1-weighted images, with corresponding lower signal on T2-weighted images, presumably because of their protein content. Dilated fluid-filled ducts are linear, radiate from the nipple, and may branch. Their signal and enhancement characteristics are the same as for cysts.

Figure 7-14 Normal variants. A, Dilated milk ducts cause linear high signal extending from the nipple (arrow) on fat-suppressed T2-weighted fast spin-echo images. B, Ducts may also demonstrate high signal (arrow) on unenhanced T1-weighted images and variable signal on T2-weighted images, presumably because of the high protein content. Unlike ductal carcinoma in situ (see Fig. 7-25), they do not enhance with contrast. C, Benign cysts cause focal, well-circumscribed high signal (large arrow) on T2-weighted images. D, Normal benign cysts do not enhance, but they may be surrounded by a faint rim of gradual enhancement (large arrow). E, Like ducts, some benign cysts may appear bright (small arrow) on unenhanced T1-weighted images.

Hormone-related enhancement occurs in premenopausal women and women taking oral contraceptives (Fig. 7-15), and is a cause for normal background enhancement, which on occasion may be moderate or marked. Usually, diffuse gradual glandular enhancement is seen, and it is commonly bilateral and symmetric. Dynamic enhancement is generally gradual and progressive (Daniel type II, III; Kuhl type I); thus, the appearance is rarely confused with invasive carcinoma on dynamic imaging. Less commonly, hormone-related enhancement may be focal (see Fig. 7-15) and may resemble lobular carcinoma or DCIS. Hormone-related enhancement is minimized by scanning during the second week of a woman’s menstrual cycle.

Figure 7-15 Hormone-related enhancement. Normal menstrual cycle variations may cause fibroglandular enhancement. A, Although hormone-related enhancement is usually mild and diffuse, it may occasionally cause focal intense enhancement that can simulate disease (arrow). Even though the persistent late enhancement suggested a benign etiology (B), repeat breast magnetic resonance imaging was performed during the second week of the menstrual cycle (C) and showed that all previous findings had resolved and were hence presumably related to menstrual cycle variations.

Fibrocystic change is commonly associated with focal (geographic) or regional nonspecific enhancement, especially in premenopausal women (Fig. 7-16), with gradual early enhancement, and with sustained gradual late enhancement. Occasionally, a specific diagnosis can be made by the presence of tiny associated microcysts (see Fig. 7-16). Adjacent cysts do not necessarily exclude carcinoma, however, so careful scrutiny of all enhancing foci remains essential to exclude concurrent malignancy.

Figure 7-16 Fibrocystic change. A, Geographic, regional, or diffuse glandular enhancement can be seen in patients with fibrocystic change. B, Although variable in appearance, the diagnosis is most readily established when small nonenhancing cysts are scattered throughout the lesion (arrow).

(A, From American College of Radiology: ACR BI-RADS®—MRI, ed 4, In ACR Breast Imaging and Reporting and Data System, breast imaging atlas, Reston, VA, 2003, American College of Radiology.)

Intramammary lymph nodes are common, especially in the upper outer quadrant and along blood vessels (Fig. 7-17). Typically, intramammary nodes are small (≤5 mm) and have uniform high T2 signal. They are sharply circumscribed oval or kidney bean-shaped masses that have a central fatty hilum. On dynamic imaging, they enhance avidly and rapidly, with a rapid initial enhancement and a late-phase plateau or early washout, and hence cannot be distinguished from malignancy based on dynamic criteria alone. However, a definitive diagnosis is usually possible when lesion morphology shows their fatty hilum and close proximity to blood vessels with a “grapes on a vine” appearance. Correlation with sonography may avoid biopsy in cases in which location or morphologic criteria remain inconclusive. MRI is not as reliable as sentinel node sampling in determining the presence or absence of intranodal metastases. Abnormal lymph nodes become rounder, enlarge from prior studies, and lose their fatty hilum. Lymphadenopathy can also be diagnosed when the node becomes completely replaced by metastases and becomes dark (instead of light) on T2.

Figure 7-17 Intramammary lymph node. Usually small and located in close proximity to superficial vessels in the upper outer quadrant and axillary tail of the breast, lymph nodes demonstrate high signal on T2-weighted images (see Fig. 7-11B). A, All lymph nodes enhance rapidly and brightly with contrast (arrow), usually with a Daniel type IV or type V time course of enhancement (B). A normal fatty hilum can cause central low signal on fat-suppressed or subtracted images that mimics rim enhancement.

Fibroadenoma is usually an oval or macrolobulated, sharply marginated, avidly and uniformly enhancing mass (Figs. 7-18 and 7-19). Young cellular fibroadenomas are very bright on noncontrast fat-suppressed T2-weighted scans. Later sclerotic fibroadenomas may be dark on T2-weighted scans. Nonenhancing internal septations are seen occasionally in about 20% of benign cellular fibroadenomas. Of note, nonenhancing internal septations may very rarely be seen in mucinous cancer, so kinetic curves on benign-appearing masses should be evaluated to distinguish fibroadenomas from T2-bright mucinous or ductal cancer. On dynamic imaging, most fibroadenomas show early gradual enhancement with sustained late gradual enhancement. Young fibroadenomas may have a more rapidly enhancing curve with sustained late-phase gradual enhancement, and they may occasionally demonstrate a late plateau of signal intensity that overlaps with the appearance of some invasive carcinomas. However, unlike many invasive carcinomas, the earliest, most avid enhancement is frequently central rather than peripheral. Among rapidly enhancing well-circumscribed masses, very high T2 signal is suggestive of benign fibroadenoma; the lack of very high T2 signal implies that malignancy cannot be excluded. The rare, well-differentiated phyllodes tumor has an appearance similar to that of fibroadenomas. Degenerating fibroadenomas, seen in older patients, do not enhance significantly and may have irregular internal signal voids that correspond to the large, coarse “popcorn” calcifications seen mammographically.

Figure 7-18 Fibroadenoma. Note the smooth, sharp margins and lobulated shape on precontrast, fat-suppressed T2-weighted images (A, arrow) and on contrast-enhanced, water-specific 3-D spectral-spatial excitation magnetization transfer gradient echo images (B, arrow). The low-signal septations (A) that do not enhance (B) are particularly specific for fibroadenoma. Frequently, magnetic resonance imaging (MRI) findings are less specific, as in this different case (C and D), which reveals an ovoid, well-circumscribed high-signal mass on T2-weighted imaging (C, arrow) that enhances very strongly (D, arrow) but without specific low-signal septations. E, The time course of enhancement is typically rapid initial enhancement followed by sustained late enhancement. MRI-guided core biopsy revealed fibroadenoma.

Figure 7-19 A, T2-weighted sagittal noncontrast magnetic resonance imaging (MRI) shows a lobulated mass with high signal intensity (arrow) in the lower breast and fluid in benign breast ducts (double arrows). Noncontrast (B) and postcontrast (C) sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) MRIs show a lobulated enhancing mass in the lower left breast that is slightly inhomogeneous but has smooth borders (arrow). D, Axial reconstruction of the 3DSSMT contrast-enhanced breast MRI shows the mass in the lower breast near the chest wall (arrow). Enhancement kinetics showed a slow uptake and late persistent curve, suggesting a benign finding. Because the patient had a history of breast cancer, she desired a biopsy of the mass. E, Second-look ultrasound of the breast shows an oval lobulated homogeneous mass (arrow) in the area of the MRI-detected mass. F, B-mode (left image) and elastography (right image) ultrasound images show that the mass (arrow) is about the same size on the strain view, suggesting a benign finding. Biopsy showed fibroadenoma.

Intraductal papilloma has a wide variety of appearances. On MRI, a papilloma may have a round masslike structure that has a rapid enhancement initial rise and washout in a late phase that is indistinguishable from breast cancer. Before MRI, most papillomas were identified by the presence of abnormal nipple discharge, an intraductal filling defect on galactography, or an intraductal mass on ultrasound. The analogous “classic” findings on MRI are an avidly enhancing mass at the posterior end of a fluid-filled duct (Fig. 7-20). However, a fluid-filled duct is not necessarily present in all cases, and dynamic enhancement spans the entire range from nonenhancing to washout curves that mimic invasive carcinoma.

Figure 7-20 Intraductal papilloma. A, Contrast-enhanced, fat-suppressed, T1-weighted, 3-D gradient echo MRI revealed a small, avidly enhancing retroareolar mass (arrow). B, A fluid-filled duct (arrowheads) extended to the mass (arrow) on precontrast, fat-suppressed T2-weighted images. Papillomas may enhance with any time course, including a rapid initial rise with a plateau mimicking invasive carcinoma. This is the classic appearance of intraductal papilloma, although not all papillomas demonstrate all these features.

(From Daniel BL, Gardner RW, Birdwell RL, et al: Magnetic resonance imaging of intraductal papilloma of the breast, Magn Reson Imaging 21:887–892, 2003.)

Postoperative changes include seroma, hematoma, scar, and fat necrosis. A careful breast history analysis usually enables distinction of these postbiopsy findings from primary breast lesions. Seroma and hematoma resemble cysts with variable intrinsic signal intensity, but they may have more irregular margins. Uniform rimlike enhancement occurs normally; peripheral nodular enhancement suggests residual tumor in the setting of pathologically transected margins. Scars and fat necrosis do not usually enhance beyond 2 years. Fat necrosis is typically manifested as irregular rimlike enhancement surrounding nonenhancing tissue that is identical to fat on all sequences.

Breast Cancers

Invasive ductal carcinoma (IDC) is virtually always manifested as a focal, avidly enhancing mass, which is often irregular but may have any shape. Margins are usually irregular or spiculated (Fig. 7-21), but IDC may be more sharply defined or smooth in some cases. Rim enhancement and enhancing internal septations are particularly suspicious. Dynamic imaging reveals rapid initial enhancement followed by a plateau or early washout of signal intensity and is frequently most worrisome at the periphery of the lesion. T2 signal is similar to that of breast tissue; the lack of high signal distinguishes IDC from benign intramammary lymph nodes and fibroadenomas. However, there are some T2-bright cancers (mucinous cancers and some invasive ductal cancers), so kinetic evaluation is important. True central nonenhancing necrosis is rare. Direct skin or muscle invasion, growth of the tumor through Cooper ligaments, and architectural distortion are secondary signs of carcinoma; axillary lymph nodes that have become rounder and lost their fatty hila are worrisome for lymphadenopathy (Fig. 7-22).

Figure 7-21 Invasive ductal carcinoma (IDC). Screening breast magnetic resonance imaging (MRI) using bilateral, dynamic, two-dimensional spoiled gradient echo images revealed focal enhancement (arrow) on the initial postcontrast scan (A) not seen on the precontrast scan (B). C, Subtraction processing confirms the suspicious enhancement (arrow). D, Repeat unilateral, water-specific, high-spatial resolution, contrast-enhanced 3-D gradient echo MRI confirmed the enhancement and revealed suspicious rim enhancement and irregular margins (arrow). E, The lesion did not have high signal on T2-weighted MRI (arrow). F, On dynamic imaging, the lesion enhanced intensely and rapidly, with a subsequent plateau of signal intensity.

Figure 7-22 Enlarged axillary lymph node. T1-weighted, precontrast spin-echo images reveal a 15-mm right axillary soft-tissue mass corresponding to an abnormally enlarged lymph node (arrow). Note the absence of a normal fatty hilum. Although magnetic resonance imaging (MRI) may reveal grossly metastatic nodes, as in this case, a normal appearance on MRI does not exclude micrometastases; the sensitivity of MRI is inferior to that of sentinel node sampling.

Infiltrating lobular carcinoma (ILC) has a much more variable appearance than IDC does. A particularly unique appearance is enhancement that follows the course of normal fibroglandular elements without a substantial mass effect (Fig. 7-23), which may lead to a missed diagnosis. ILC can also appear as a solitary mass or a combination of multiple masses with or without enhancing intervening fibroglandular tissue. Rarely, ILC may not enhance enough to be distinguished from surrounding breast tissue. On dynamic imaging, lobular carcinoma may have any pattern; benign patterns of dynamic curves, such as either slow or rapid initial enhancement with sustained late-phase gradual enhancement, do not exclude lobular carcinoma.

Figure 7-23 Infiltrating lobular carcinoma. A, Contrast-enhanced, water-selective, 3-D gradient echo images reveal enhancement along the normal fibroglandular elements (arrows), without a significant mass effect, findings corresponding to the infiltrating pattern of spread. B, Initial enhancement is rapid but is followed by sustained late enhancement.

Mucinous carcinoma, a rare breast cancer, is a round mass that may have a unique appearance on MRI (Fig. 7-24). The large central pool of mucin does not enhance and has very high T2 signal. Thus, mucinous carcinoma resembles a cyst, but with an irregular, thickened, avidly enhancing rim. Breast abscess may have a similar appearance. Alternatively, it may have irregular internal enhancement.

Figure 7-24 Mucinous carcinoma. Axial, fat-suppressed T2-weighted fast spin-echo images reveal a high-signal lesion (A, arrow) with surrounding rim enhancement (arrow) on sagittal water-specific 3-D gradient echo images (B). C, Although the dynamic enhancement of the rim is indeterminate, the nodularity and irregular thickness of the rim are incompatible with a simple cyst. Biopsy revealed invasive carcinoma with mucinous features.

DCIS has a very wide range of appearances on MRI. The “classic” description is clumped enhancement in a ductal system distribution, including segmental enhancement, or linear/branching enhancement emanating from the nipple (Fig. 7-25). Ductal enhancement per se is present in only a minority of cases. An especially worrisome sign for DCIS includes clumped enhancement, which represents enhancement tumor following the duct, simulating a string of pearls or cobblestone appearance. This is due to the cancer growing and expanding the ductal system, without penetrating the duct basement membrane.

Figure 7-25 Ductal carcinoma in situ (DCIS). A, Sagittal high-spatial resolution water-selective 3-D magnetic resonance imaging (MRI) reveals enhancement in a segmental distribution corresponding to one ductal system (arrows). B, Dynamic 3-D spiral MRI reveals a small focus that enhanced on the initial images (arrow) sooner than the rest of the lesion, which enhanced on later images (C). D, This small focus, which had a washout curve, proved to be a 4-mm focus invasive ductal carcinoma within the DCIS. IDC, invasive ductal carcinoma.

DCIS also can be manifested as a focal area of clumped enhancement, as a focal mass, as geographic nonspecific enhancement, or even as enhancement indistinguishable from other breast tissue. Dynamic enhancement is also unreliable. DCIS usually enhances with a nonspecific rapid initial enhancement and a sustained gradual enhancement curve. However, any curve type can be seen, including no enhancement or suspicious rapid initial enhancement with a late-phase plateau or early washout. Thus, DCIS may resemble focal fibrocystic change, hormone-related enhancement, intraductal papilloma, or even invasive carcinoma. When associated with an invasive tumor, DCIS commonly appears as a surrounding wedge of enhancing tissue that has a less worrisome dynamic enhancement curve than do invasive tumors. Calcifications cannot be reliably assessed with MRI, and thus mammographic correlation remains essential when attempting to determine the extent or presence of disease. Of note, between 25% and 40% of DCIS may be diagnosed only by pleomorphic calcifications seen on mammography in DCIS that is invisible on the contrast-enhanced MRI. Thus, it is important to biopsy pleomorphic calcifications if they are of concern for cancer because they may be the only sign of malignancy.

Diagnostic Limitations

Although the sensitivity of MRI is very high for invasive carcinoma, significantly higher than mammography or sonography in some settings, substantial diagnostic challenges remain (see Boxes 7-9 and 7-10). Common false positives mimicking DCIS include focal fibrocystic change, hormone-related enhancement, focal fibrosis, and fibroadenomatous change. False positives occasionally mimicking invasive carcinomas include rapidly enhancing intraductal papillomas, avidly enhancing fibroadenomas lacking high T2 signal, intramammary lymph nodes without a fatty hilum, rim-enhancing fat necrosis, radial scar, and enhancing spiculated surgical scars. False negatives remain rare; they are usually due to nonenhancing DCIS or ILC. Recent or ongoing chemotherapy may also reduce the sensitivity of contrast-enhanced MRI.

Small incidental enhancing lesions (IELs) are foci that are smaller than 5 mm, difficult to characterize, and common. Investigators vary in the level of concern they attribute to these lesions. Regardless of size, an initial attempt should be made to characterize each lesion’s morphology, dynamic enhancement, and T2 signal because invasive carcinomas, fibroadenoma, and papilloma can also be very small. However, biopsy of an IEL frequently reveals no identifiable explanation. A practical approach to management is to use both the character of individual lesions along with their number and distribution, as well as the patient’s clinical setting to determine whether biopsy or follow-up MRI should be performed. In patients at very high risk for occult breast malignancy, such as those with known axillary nodal metastases and normal mammograms and physical examination, even a single relatively nonspecific IEL that is the dominant abnormality in the breast may be the index tumor and should prompt biopsy. In patients with lower risk, multiple bilateral, diffusely scattered, nonspecific small IELs have been successfully managed with serial MRI to document stability.

Screening

Improvements in genetic testing and counseling are identifying an increasing population of women who are at increased risk for the development of breast cancer. Current options include routine clinical and imaging screening with mammography or ultrasound and prophylactic mastectomy. MRI has recently been investigated as an adjunct to conventional imaging for screening. In one of the largest U.S. studies, Morris and colleagues detected 14 tumors in 367 BRCA1 and BRCA2 mutation carriers, individuals with a similar risk profile and negative initial mammograms (Fig. 7-26). This led to the 2007 recommendation by the American Cancer Society for cancer screening with MRI in the United States in women with a greater than 20% lifetime risk of breast cancer and in patients who have a history of treated Hodgkin disease (Table 7-7). Optimal MRI screening intervals and the age at which MRI screening should be initiated have yet to be determined.

Figure 7-26 Ductal carcinoma in situ (DCIS) detected on screening magnetic resonance imaging (MRI). MRI was performed after genetic testing revealed a suspicious BRCA1 mutation. A, An 8-mm focal area of enhancement was noted with irregular margins on high-spatial resolution MRI (arrow). B, Dynamic imaging demonstrated a nonspecific enhancement curve. Pathologic examination revealed a 6.9-cm region of high-grade comedo DCIS.

Women without a documented increased risk for breast cancer benefit less from MRI because the rate of false-positive abnormalities may substantially exceed the rate at which cancers are found; further investigation of these false-positive results may subject these women to significant morbidity. Patients with a history of direct free silicone injections of the breast for augmentation, however, cannot undergo any other type of screening (i.e., clinical breast examination, mammography, or sonography) with confidence and hence may be appropriate screening subjects when counseled accordingly about the risks associated with false-positive lesions.

Diagnosis

MRI is infrequently used to diagnose equivocal findings on mammography, sonography, or physical examination because the cost of MRI, including follow-up MRI, approaches the cost of the more traditional minimally invasive core biopsy. However, in rare instances, lesions are found that are not amenable to conventional biopsy, such as suspicious findings seen on only one mammographic view (Fig. 7-27). MRI is also used to evaluate patients with persistent bloody or cytologically abnormal nipple discharge in whom conventional galactography and ductoscopy were either unrevealing or unsuccessful. In addition, MRI is used to evaluate patients with equivocal findings on physical examination that are mammographically and sonographically occult. However, the potential for false-positive and equivocal findings that generate biopsy or follow-up MRI must be balanced against the accuracy of simple palpation-based biopsy in this setting.

Figure 7-27 Magnetic resonance imaging (MRI) of a suspicious mass seen on one x-ray mammographic view. A, A suspicious mass was noted in the superior aspect of the breast, near the chest wall on the mediolateral oblique (MLO) mammogram only (arrow). B, Water-selective 3-D gradient echo MRI revealed a focal enhancing mass (arrow). Preoperative MRI-guided wire localization was performed (not shown). C, After localization, an MLO mammogram confirmed that localization was successful and the lesion (arrow) was too close to the chest wall to be seen on craniocaudal views (D). Pathologic evaluation revealed a small fibroadenoma.

(From Offodile RS, Daniel BL, Jeffrey SS, et al: Magnetic resonance imaging of suspicious breast masses seen on one mammographic view, Breast J 10(5):416–422, 2004.)

Staging

MRI is frequently used preoperatively to image the extent of biopsy-proven breast cancer, especially in patients contemplating breast-conserving therapy. Controversy exists over whether all patients who have breast cancer should undergo breast MRI as part of the staging process. In fact, several articles indicate that the MRI may cause false-positive biopsies as well as fail to improve the resection rate at the first surgery. However, although not routinely indicated as part of the local staging process in all newly diagnosed carcinomas, MRI is commonly used in selected subgroups, including the following:

Figure 7-28 Mammographically occult breast cancer in a patient with axillary node metastases. Mediolateral oblique (A) and craniocaudal (B) mam-mograms revealed only postoperative changes in the right axilla (A, arrows) in this patient with a history of metastatic breast cancer discovered on recent excision of a palpable axillary node. C, Sagittal water-selective contrast-enhanced magnetic resonance imaging (MRI) revealed an 11-mm focal mass in the lateral portion of the breast (arrow). MRI-guided, wire-localized excision revealed a 9-mm invasive ductal carcinoma that was excised with tumor-free margins.

Figure 7-29 Chest wall invasion. Contrast-enhanced, 3-D water-specific breast magnetic resonance imaging reveals a large spiculated mass in the posterior of the breast. The enhancing tissue traverses the normal retromammary fat plane to abut the chest wall. The focal enhancement of the pectoralis muscle (arrow) is consistent with invasion and indicates locally advanced disease.

(From American College of Radiology: ACR BI-RADS®—MRI, ed 4, In ACR Breast Imaging and Reporting and Data System, breast imaging atlas, Reston, VA, 2003, American College of Radiology.)

In these patients, MRI may be used to plan the shape of the lumpectomy in an attempt to minimize the chance of transecting tumor margins. MRI may also reveal mammographically occult multifocal carcinoma (Fig. 7-30) and thereby prompt wider local excision. In addition, MRI may reveal occult multicentric or bilateral carcinoma (Fig. 7-31). Recent papers indicate that mammographically occult contralateral carcinoma is detected in 3.8% to 5.4% of patients with unilateral carcinoma. In these circumstances, preoperative biopsy is critical to pathologically confirm multicentric carcinoma or bilateral carcinoma because MRI findings can be nonspecific and may even lead to more extensive surgery than necessary in occasional patients.

Figure 7-30 Multifocal carcinoma. Water-specific, contrast-enhanced 3-D magnetic resonance imaging (MRI) revealed multiple suspicious enhancing masses in the upper outer quadrant (arrows), as shown on these 2-cm–thick slab, maximum intensity projections in the sagittal (A) and axial (B) planes. MRI-guided lumpectomy confirmed multifocal invasive carcinoma.

Figure 7-31 Multicentric and contralateral breast lesions. A, Water-selective magnetic resonance imaging (MRI) confirmed a 1.5-cm palpable invasive ductal carcinoma in the lower outer portion of the right breast (arrow) of a patient with normal bilateral mammograms. B, In addition, a suspicious upper inner quadrant enhancing focus (arrow) was shown to be stromal fibrosis and fibrocystic changes by MRI-guided, wire-localized biopsy. C, MRI of the asymptomatic left breast also demonstrated a brightly enhancing focus (arrow) that proved to be an 8-mm invasive ductal carcinoma at MRI-guided biopsy.

Although MRI is most easily interpreted when performed in the absence of recent surgery because of the potential overlap of postsurgical healing scars and imaging findings of tumor, it has been successfully used to map the extent of residual disease in patients with transected tumor detected at the margins of an initial excisional biopsy specimen. Asymmetric and nodular enhancement or enhancement that is noncontiguous with the biopsy site is suspicious.

Formal outcome studies demonstrating the benefit of staging MRI as an adjunct to conventional breast-conserving therapy are still in progress; however, controversy persists regarding the exact role and benefit of staging breast cancer by MRI given the high success rate of traditional breast-conserving therapy without MRI.

Management

Patients undergoing neoadjuvant chemotherapy are frequently imaged with breast MRI. Pretreatment scans provide the most accurate nonsurgical 3-D measurements of the extent of tumor. Scans performed after the first one or two cycles can detect a treatment response that may predict whether completion of chemotherapy will be successful. In patients who do respond, MRI after completion of chemotherapy can be used to identify and localize residual tumor, even in patients who have had a complete clinical response (Fig. 7-32). It is important to note that in these circumstances, the dynamic enhancement of tumors may be less specific and may even resemble benign disease. Indeed, any residual enhancement at the site of a previously known tumor is suspicious. Because of the poor specificity of MRI findings after chemotherapy, pretreatment MRI is essential as a baseline for comparison.

Figure 7-32 Response to neoadjuvant chemotherapy. A, Initial contrast-enhanced, water-selective 3-D gradient echo magnetic resonance imaging (MRI) confirmed a discrete, central avidly enhancing mass approximately 2.5 cm in diameter consistent with biopsy-proven invasive ductal carcinoma (arrow). B, Follow-up MRI after a complete clinical response to neoadjuvant chemotherapy revealed a small residual mass (arrow). C, Note that after chemotherapy, the time course of contrast enhancement of the residual tumor had a benign shape, a marked change in comparison to the suspicious pretreatment curve.

MRI has also been investigated for its ability to detect local breast cancer recurrence. Debate persists regarding the duration of enhancement in benign postsurgical scars, although enhancement clearly decreases substantially over the first 2 years. Nevertheless, interpretation is best performed on serial MRI scans to assess whether enhancement is normally decreasing over time or suspiciously increasing over time.

Second-Look Ultrasound

Lesions that are detected by MRI must frequently be biopsied (Box 7-12). The easiest method of biopsy is to perform a “second-look” ultrasound examination directed toward the specific area of abnormality noted on MRI. If a corresponding lesion is seen, ultrasound-guided core needle biopsy is easily performed. Careful attention to technique is essential to ensure that the MRI abnormality corresponds to the sonographic lesion, given the difference in patient position and breast configuration between the two methods.

Studies evaluating MRI-detected findings with sonography show that ultrasound demonstrates a finding in between 23% and 90%. A 2010 study by Abe and colleagues showed that 57% (115/202) of MRI-detected findings were seen by ultrasound. Of the remaining 87 lesions undetected by ultrasound, II were cancer. Other studies by Ko and colleagues (2007), Linda and colleagues (2008), and Destounis and colleagues (2009) showed that 90%, 82%, and 70% of 10, 173, and 182 MRI-detected findings, respectively, were seen on second-look ultrasound.

The largest study designed to evaluate which MRI lesion should undergo targeted ultrasound for purposes of biopsy, Meissnitzer and colleagues showed in 2009 that 290 of 519 MRI-detected lesions (56%) were seen with second-look ultrasound, with masses more likely to be seen compared to nonmass lesions (62% of masses versus 31% of nonmass lesions). This study showed that MRI-detected lesions were most likely to be seen with ultrasound if the MRI finding was a mass (rather than a nonmass), if it was large, if it was BI-RADS® category 5, if the mass had rim enhancement, or if it was a nonmass with clumped enhancement. Furthermore, Meissnitzer’s study showed that 10 of 80 findings were discordant on a follow-up MRI after ultrasound-guided biopsy for second-look sonographic findings thought to represent the MRI target. This means that the “concordant” second-look ultrasound biopsy did not sample the MRI-detected abnormality. Of the 9 out of 10 patients who underwent subsequent MRI-guided core biopsy, 5 had cancers. For these patients, biopsy must be performed under direct MRI guidance.

Preoperative Needle Localization

The simplest method of MRI-guided biopsy is preoperative MRI-guided needle localization and hookwire marking (Fig. 7-33). With the use of an open breast coil and sterile technique, an 18- or 20-gauge MRI-compatible needle is inserted in the breast and directed toward the abnormality. A variety of methods have been proposed to determine the correct needle trajectory, including grid-coordinate positioning devices and freehand methods. Contrast-enhanced scans are critical to confirm correct needle placement and target localization. Procedure speed is important because lesions commonly do not enhance preferentially over breast tissue more than 5 to 10 minutes after injection.

Figure 7-33 Magnetic resonance imaging (MRI)-guided needle localization. A, Axial, contrast-enhanced, water-selective two-dimensional gradient echo MRI reveals an MRI-compatible localizing needle abutting the suspicious focus of contrast enhancement (arrow) described in Figure 7-28. B, An axial T1-weighted fast spin-echo image after hookwire deployment reveals the mass centered on the stiffener of the hookwire (arrow). C, Radiography of the excised specimen demonstrated nonspecific glandular tissue adjacent to the hookwire (arrow). Pathologic examination revealed invasive ductal carcinoma.

A postprocedure, presurgery mammogram is recommended for three reasons. First, most breast surgeons are more familiar with the use of mammograms in planning the surgical approach. Second, mammography may reveal a mass or calcifications at the MRI-guided, wire-localized lesion that was not previously appreciated as suspicious and can therefore be looked for on intraoperative specimen radiographs, thus maximizing the chance for accurate surgical excision. Third, mammograms document the location of the MRI-guided biopsy and hence provide a critical baseline for future postoperative mammograms.

Correlating the MRI, mammographic, and ultrasound finding can be challenging. Use of markers or clips after core biopsy can be extremely helpful to identify findings cored under ultrasound, MRI, or stereotactic core biopsy, especially if the patient is to undergo excision of cancer seen on more than one modality (Fig. 7-34).

Figure 7-34 Core biopsy and needle localization of invasive ductal cancer (IDC) and ductal carcinoma in situ (DCIS) on postcontrast sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) magnetic resonance imaging (MRI) scans and ultrasound. A, Ultrasound shows a palpable spiculated mass (arrow) in the upper outer quadrant of the right breast, worrisome for cancer. B, Ultrasound-guided core biopsy showed IDC. C, Ultrasound showing marker (arrow) placement during the core biopsy. Craniocaudal (CC) (D) and mediolateral oblique (E) digital mammograms after the core biopsy show the marker in the upper outer right breast in a suspicious spiculated mass (arrows). Biopsy showed IDC. F, Postcontrast sagittal 3DSSMT MRI scan shows linear enhancement extending from the midbreast to the chest wall. There is a signal void (arrow) in the thickened portion of enhancement, representing the biopsied cancer and the marker placed by ultrasound. The corresponding region of interest (G) and kinetic curve (H) show rapid initial enhancement and washout compatible with the known invasive cancer. I, In an adjacent sagittal MRI slice, the linear enhancement extends anterior and posterior to the known cancer (arrows), worrisome for DCIS, even though kinetic enhancement curves were unremarkable. To determine if the linear enhancement represented DCIS, an MRI-guided core biopsy was done. J, Three-point Dixon axial postcontrast MRI during a vacuum-assisted, MRI-guided core biopsy shows the invasive cancer and signal void in the posterior breast (arrow). Three-point Dixon axial (K) and sagittal (L) postcontrast MRI slices shows the 10-gauge obturator and sheath (dark linear signal void; arrow) traversing the linear enhancement about 3 cm anterior to the IDC during an MRI-guided core biopsy. After the core biopsy a ring-shaped marker was placed in the biopsy site under MRI guidance. Core biopsy showed DCIS.CC (M) and mediolateral (N) mammograms after MRI-guided biopsy show the ring-shaped metal marker (arrow) within the biopsy site (DCIS). Note the known cancer and marker posteriorly, near the chest wall (arrows). MRI-guided bracket needle localization of the linear enhancement was recommended to include both the IDC and the linear enhancement. O, The postcontrast three-point Dixon preoperative needle localization axial MRI scan shows a wire signal void traversing the posterior invasive cancer (arrow) and a wire traversing the anterior aspect of the linear enhancement (P), bracketing the area to be excised. Q, Sagittal preoperative needle localization axial MRI scan shows the signal void from the bracketing wires of the posterior mass and the anterior edge of the ductal enhancement (arrows). CC (R) and mediolateral (S) mammograms after MRI-guided needle localization show the posterior wire is superior to the spiculated mass by at least 2 cm; the surgeon could possibly miss the IDC (arrows). It was decided to place a third wire into the IDC by ultrasound. T, Ultrasound-guided needle localization of the spiculated mass shows a wire passing to the mass. CC (U) and mediolateral (V) mammograms after ultrasound-guided needle localization show a third wire in the spiculated mass on films marked for the surgeon. W, Specimen radiograph shows inclusion of three hookwires, three hookwire tips, and the two markers (arrows). Pathology showed IDC and DCIS.

On occasion, the target may not be seen during the preoperative needle localization procedure. This may be due to a variety of reasons, including vigorous breast compression, which does not allow inflow of contrast material to enhance the lesion; spurious enhancement of a lesion due to hormonal influences; or nonvisualization for unknown reasons. In most cases, definite localization can proceed based on surrounding breast architecture rather than targeting the enhanced lesion if such architecture exists. Otherwise, a 1-month follow-up contrast-enhanced MRI study will confirm or exclude whether the enhancing lesion still exists. On occasion, breast cancers may not enhance on the day of preoperative needle localization. In these cases, the short-term MRI follow-up may be helpful to confirm the lesion, and that the need for biopsy still exists.

Based on published data, contrast-enhanced breast MRI preoperative needle localization true-positive results range between 20% and 40%, similar to mammographically detected breast lesion needle localization data.

Percutaneous Core Biopsy

Percutaneous core needle biopsy (Fig. 7-35) can be performed under direct MRI guidance by both grid-coordinate and freehand methods. Devices include MRI-compatible 14-gauge titanium needles and vacuum-assisted biopsy devices. The imaging artifacts associated with core biopsy needles and the potential for breast motion remain limitations to reliable biopsy of sub-centimeter lesions given the current technology.

Figure 7-35 Magnetic resonance imaging (MRI)-guided vacuum-assisted core needle biopsy. Axial, water-selective, two-dimensional gradient echo MRI revealed the inner trocar of a 14-gauge titanium biopsy needle extended through the focally enhancing mass (arrow) noted in Figure 7-19C to E. Pathologic evaluation revealed benign fibroadenoma.

MRI-guided core biopsy can be especially helpful after a breast cancer diagnosis if MRI detects a possible second cancer not seen on any other modality. This is particularly true in the postbiopsy surgical patient who has already undergone one operation and now seeks definitive surgical therapy (Fig. 7-36).

Figure 7-36 Magnetic resonance imaging (MRI)-guided core biopsy for incidental enhancing lesion (IEL) after lumpectomy for invasive ductal cancer (IDC). This patient had a lumpectomy for IDC, resulting in a seroma in the posterior breast. The MRI was done to look for additional foci of cancer. A, Postcontrast sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) MRI scan shows the seroma (arrows) and a nonspecific mass 3.5 cm anterior to the seroma. The region of interest (ROI) (B) and corresponding kinetic curve (C) show rapid initial enhancement and plateau, worrisome for cancer. Note, two ROI were placed on the slice because the patient moved between the two scans: one line represents the initial kinetic curve for the lesion; the other line represents the kinetic curve for the late, “wash-out” phase. This shows that motion artifact can have spurious results if motion correction is not employed. To determine if the IEL was cancer, MRI-guided core biopsy was done. D, Axial T1-weighted nonfat-suppressed noncontrast MRI shows the needle (arrow) adjacent to the expected location of the IEL based on reconstructed axial images from the diagnostic 3DSSMT MRI. Incidentally, note the seroma in the posterior aspect of the breast (double arrows). E, Sagittal three-point Dixon postcontrast MRI-guided vacuum-assisted core biopsy scan shows signal void (arrow) adjacent to the IEL in the anterior breast. In this case, the needle biopsy trough is aimed toward the patient’s chest wall to sample the IEL. Note the seroma from excisional biopsy for IDC (double arrows), rim enhancement around the biopsy site, the fluid/fluid level, and the fibrin ball in the superior aspect of the cavity. F, Axial three-point Dixon postcontrast MRI shows the needle (arrow) adjacent to the IEL. Core needle biopsy showed a second focus of IDC.

MRI-compatible clips may be deployed after MRI-guided core needle biopsy to mark the site of biopsy. When benign results are obtained that do not specifically correspond to the expected appearance of the MRI lesion, repeat MRI-guided needle-localized surgical biopsy or follow-up MRI must be performed. The use of the MRI-guided markers or markers placed under ultrasound that are later imaged by MRI or mammography can help guide the surgeon to excise the entire tumor and any associated DCIS (Fig. 7-37).

Figure 7-37 Correlation of mammography, ultrasound, and 3 Tesla (T) magnetic resonance imaging (MRI) for needle localization. A, Lateral mammogram in a 72-year-old woman with a palpable mass in the outer left breast shows a dense mass (arrow) in the midbreast at the 3-o’clock position. B, Magnified cropped left craniocaudal mammogram shows the spiculated mass (arrow) and curvilinear area of dense tissue lateral and anterior to the spiculated mass (arrows). This curvilinear density was later shown to represent noncalcified ductal carcinoma in situ (DCIS). C, Lateral cropped magnification mammogram shows the spiculated mass (arrow) and curvilinear density extending superior to the mass (arrows). D, Shaded cut surface display postcontrast 3T 3-D spectral-spatial excitation magnetization transfer (3DSSMT) MRI shows a spiculated mass with clumped enhancement extending superiorly in a curvilinear distribution, corresponding to the findings shown on the mammograms in parts B and C. E, Maximal intensity projection (MIP) 3DSSMT MRI shows the mass and clumped enhancement representing invasive ductal cancer and DCIS on biopsy. Note scattered foci of nonspecific enhancement elsewhere in the breast. F, Thick slab MIP cut surface display shows the invasive ductal cancer, associated DCIS, and axillary adenopathy in greater detail. G to I, Thick slab axial reconstructions of breast cancer and DCIS. Three slices from axial reconstruction 3T MRI show the irregular invasive ductal cancer mass (arrow) and clumped ductal enhancement DCIS extending from the mass (double arrows), corresponding to the mammographic findings on the craniocaudal mammogram in part B. J, Second-look ultrasound directed to the left breast shows the invasive ductal cancer seen on the MRI and on the mammogram. K, Second-look ultrasound superior to the cancer shows nodular hypoechoic ductal findings corresponding to the clumped DCIS enhancement seen on MRI. Ultrasound-guided core biopsy of the nodular hypoechoic ductal findings showed DCIS. A marker was placed in the DCIS under ultrasound. Scout annotated lateral mammogram for preoperative needle localization (L) and scout craniocaudal mammogram (M). Of note, a calcified benign-appearing mass was also cored under ultrasound superior to the cancer and found to be benign. The invasive cancer and the DCIS were localized under x-ray guidance using mammographic landmarks, and invasive ductal cancer and DCIS with clear margins were found at surgery.

Diffusion-Weighted MRI

Diffusion-weighted imaging (DWI) measures water molecule mobility in vivo on unenhanced breast MRI sequences (Fig. 7-38). DWI evaluates tissue biophysical characteristics, such as the microstructure of breast tissue, cell density, membrane integrity, and extracellular matrix composition. Preliminary studies show a lower apparent diffusion coefficient (ADC) on DWI studies of breast cancers (Table 7-8). A higher ADC was observed in benign breast lesions and normal tissue. It was thought that a higher cell density in breast cancer causes an increased restriction of the extracellular matrix, with the resultant increased signal fraction coming from intracellular water. A preliminary study by Partridge and colleagues showed that increased positive predictive value might be achieved by combining ADC and conventional contrast-enhanced MRI criteria. The studies will need to be validated with larger populations.

Figure 7-38 A 65-year-old woman with invasive ductal cancer of the right breast seen on diffusion-weighted imaging (DWI). A, Noncontrast DWI spin-echo echoplanar image obtained with a b-value of 600 at 3.0 Tesla (TR/TE 2000/76 ms, matrix 128 × 256, with 8 signal averages, 5-mm slice thickness). An invasive ductal cancer is present in the right breast and is high signal on the DWI (arrow). The restricted diffusion in the tumor leads to intrinsically high signal intensity even before contrast administration. B, For comparison, subsequent high spatial resolution water-selective T1-weighted contrast-enhanced 3-D spoiled gradient echo image of the same breast cancer (arrow).